恶性肿瘤的瘤苗免疫治疗

恶性肿瘤的瘤苗免疫治疗 ,是指应用肿瘤细胞或经各种基因修饰后的肿瘤细胞在体外制成瘤苗 ,经致死性剂量照射后 ,重新接种于患者体内 ,使逃避免疫监视的肿瘤细胞可以被免疫系统识别 ,从而诱导机体产生针对肿瘤细胞的主动的、特异性的免疫反应。目前 ,瘤苗免疫治疗已有很多成功的动物模型 ,人体的临床试验也取得了肯定的疗效。但如何进一步提高免疫效果 。

Transfection of the Human Sodium/Iodide Symporter(NIS) Gene with Liposomes and the Expression of the NIS Protein in Human Lung A549 Cancer Cells

OBJECTIVE To examine the possibility of human sodium iodide symporter （hNIS） protein expression in lung cancer cells. METHODS Human lung A549 cancer cells were thawed and cultured in vitro. The cells were divided into an experimental group transfected with a recombinant pcDNA3-hNIS plasmid and a control group transfected only with a pcDNA3 plasmid. The recombinant plasmid vector encoding the hNIS gene （pcDNA3-hNIS） was amplified, purified and identified. The hNIS gene was followed by DNA sequencing. A Western blot and an immunohistochemical assay were applied to detect the hNIS protein expression in the transfected human lung A549 cancer cells. RESULTS Restriction enzyme digestion and DNA sequencing results showed the size and direction of the inserted gene in the recombinant pcD- NA3-hNIS plasmid was correct. The Western blot method and immunohistochemical analysis showed a positive NIS protein expression in the experimental group. The NIS protein was detected mainly in the cell membranes showing a positive rate up to 70.6% with no expression of the NIS protein in the control group. There was a significant difference between two groups （P=0.000）. CONCLUSION The hNIS gene was transfected effectively into human lung A549 cancer cells mediated by Lipofectamine 2000, and was expressed with its protein in vitro.

KAI1 is a potential target for anti-metastasis in pancreatic cancer cells

AIM: To investigate whether KAI1, as a metastasis suppressor gene, is associated with invasive and metastatic ability of pancreatic cancer cells.METHODS: KAI1 gene was transfected into pancreatic cancer cell line MiaPaCa Ⅱ by liposomes selected with G418. Expression of transfected cells was measured by Western blotting, immunofluorescence and immunocytochemistry. Tumor cell invasion and metastatic ability were detected through gelatinase activity and reconstituted basement membrane (Matrigel) assay. pCMV-KAI1 was directly injected into the heterotopic human pancreatic adenocarcinoma successfully established in the groin of BALB/C nude mice, by subcutaneous injection of MiaPaCa Ⅱ pancreatic cancer cells. The statistical analysis between groups was determined by Student's two tailed t test.RESULTS: By Western blotting, MiaPaCa Ⅱ cells transfected by KAI1 gene indicated KAI1 expression at approximately 29.1 kDa. Cytoplasm staining was positive and uniformly spread in transfected cancer cells, using immunohistochemistry and immunofluorescence. The most obvious difference was present after 30 h (MiaPaca Ⅱ 43.6 ± 9.42, pCMV-MiaPaca Ⅱ 44.8 ± 8.56, pCMV-KAI1-MiaPaca Ⅱ 22.0 ± 4.69, P < 0.05). Gelatinolysis revealed a wider and clearer band of gelatinolytic activity in non-transfected than in transfected cells (MiaPaCa Ⅱ cells 30.8 ± 0.57, transfected cells 28.1 ± 0.65, P < 0.05). In vivo tumor growth rates of KAI1 transfectants with KAI1-Lipofectamine 1.22 ± 0.31 in A group were lower than control 4.61 ± 1.98 and pCMV-KAI 11.67 ± 0.81. Analyses of metastases with and without KAI1 transfection in mice were different in liver and lung between controls 1.62 ± 0.39, 0.45 ± 0.09, pCMV-KAI 1.01 ± 0.27, 0.33 ± 0.09 and KAI1-Lipofectamine 0.99 ± 0.21, 0.30 ± 0.09 respectively (P < 0.05).CONCLUSION: High expression of KAI1 gene was found in transfected MiaPaCa Ⅱ human pancreatic cancer cells with lower metastatic ability. KAI1 gene plays an important role in inhibiting metastasis of pancreatic cancer after direct injection into pancreatic adenocarcinoma. These results show that the suppressed invasion and motor function of pancreatic cancer cells may be a key reason why the KAI1 gene controls pancreatic cancer cell metastasis.

Identify lymphatic metastasis-associated genes in mouse hepatocarcinoma cell lines using gene chip

AIM: In order to obtain lymphogenous metastasisassociated genes, we compared the transcriptional profiles of mouse hepatocarcinoma cell lines Hca-F with highly lymphatic metastasis potential and Hca-P with low lymphatic metastasis potential.METHODS: Total RNA was isolated from Hca-F and Hca-P cells and synthesized into double-stranded cDNA. In vitro transcription double-stranded cDNA was labeled with biotin (i.e. biotin-labeled cRNA, used as the probe). The cRNA probes hybridized with Affymetrix GeneChip() MOE430A (containing 22 690 transcripts, including 14 500 known mouse genes and 4 371 ESTs) respectively and the signals were scanned by the GeneArray Scanner. The results were then analyzed by bioinformatics.RESULTS: Out of the 14 500 known genes investigated,110 (0.8%) were up regulated at least 23 fold. Among the total 4 371 ESTs, 17 ESTs (0.4%) (data were not presented) were up regulated at least 23 fold. According to the Gene Ontology and TreeView analysis, the 110genes were further classified into two groups: differential biological process profile and molecular function profile.CONCLUSION: Using high-throughput gene chip method,a large number of genes and their cellular functions about angiogenesis, cell adhesion, signal transduction, cell motility, transport, microtubule-based process, cytoskeleton organization and biogenesis, cell cycle, transcription,chaperone activity, motor activity, protein kinase activity,receptor binding and protein binding might be involved in the process of lymphatic metastasis and deserve to be used as potential candidates for further investigation.Cyclin D1, Fosl1, Hsp47, EGFR and AR, and Cav-1 are selected as the possible candidate genes of the metastatic phenotype, which need to be validated in later experiments.ESTs (data were not presented) might indicate novel genes associated with lymphatic metastasis. Validating the function of these genes is helpful to identify the key or candidate gene/pathway responsible for lymphatic metastasis, which might be used as the diagnostic markers and the therapeutic targets for lymphatic metastasis.

Adenoviral gene therapy in gastric cancer: A review

Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors. Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.

Effects of Exogenous CC10 Transfection on CyclinDl Protein and mRNA Expression in A549 Lung Cancer Cells

Objective： To investigate the effects of exogenous CC10 gene transfection on cell cycle and the expression of cyclinD1 protein and mRNA in A549 cells. Methods： A549 cells in all test groups （group A to E） and control group （group F） were transfected with exogenous CC10 gene by liposome for 8, 16, 24, 36, 48 and 0 h respectively. CC10 protein expression was detected in A549 cells by Western blot. The growth inhibitory rate was detected by MTT method. Flow cyometry analysis （FCS） and AnnexinV-PI staining were used to determine the changes of cell cycle progression and apoptosis rate in all groups. CyclinD1 protein and mRNA expression in A549 cells was detected by the methods of immunocytochemistry and RT-PCR. Results： Exogenous CC10 gene could inhibit the growth of A549 cells, and the growth inhibitory rates in all test groups （from group A to E） were 24.7%, 33.1%, 44.3%, 61.7% and 74.2% respectively, and that in group F was 6.24%. CC10 blocked the cell cycle progression at G0/G1 and induced apoptosis gradually. In A549 cells of test groups, the expression of cyclinD1 protein and mRNA was significantly decreased. Conclusion： The inhibitory effects of the transfection of exogenous CC10 gene on G0/G1 cycle of lung cancer cells might be related with the down-regulation of cyclinD1 gene.

Transfection of apoptosis related gene Fas ligand in human hepatocellular carcinoma cells and its significance in apoptosis

AIM: To evaluate the expression of apoptosis related gene Fas ligand (FasL) in human hepatocellular carcinoma (HCC) cells HepG2 and its significance in apoptosis. METHODS: Levels of soluble Fas ligand (sFasL) in a group of patients with hepatitis B virus (HBV)-induced chronichepatitis, HBV-positive liver cirrhosis and HCC were evaluated. In a further study, the recombinant eukaryotic expression plasmid pcDNA3.1hisB-FasL was transfected into HCC cells HepG2 by lipofection, and then soluble FasL was examined in the supernatant of culture cells by EIA, FasL expression in HepG2 cells was detected by immuohistochemistry. After being stained by annexin V and propidium iodine, cells were passed through a flow cytometer and examined by a fluorescence microscope and a laser scanning microscope.RESULTS: The sFasL levels were significantly lower in patients with HCC when compared to the patients with hepatitis or liver cirrhosis. In comparison with untransfected cells, the soluble FasL could be detected in the supernatant of transfected cells. FasL was expressed on the membranes and cytoplasm of transfected cells. The apoptotic cell rate was 36.30% in transfected cells, and was 11.53% in untransfected cells. Moreover, the different stage of apoptotic cells could be distinguished by annexin V and propidium iodine staining.CONCLUSION: Fas ligand is an apoptotic pathway of HCC cells.

Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene

AIM:To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS:We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family,member 1 (ING1) expression. RESULTS:Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentia-tion and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion,tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION:These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.

Enhanced anti-tumor immunity ex vivo induced by GM-CSF gene transducted dendritic cell vaccine

Objective： The aim of the study was to investigate whether dendritic cell （DC） precursors, recruited by injection of chemokine ligand 3 （CCL3）, induce enhanced anti-tumor immunity after granulocyte-macrophage colony stimulating factor （GM-CSF） transfection in mice ex vivo. Methods： The 615 mice were injected with CCL3 via the tail vein. Freshly isolated B220–CD11c＋ cells were cultured with cytokines. For adenoviral （Ad）-mediated gene transduction, DCs were transferred AdGM-CSF gene at different ratios of multiplicity of infection （MOI） to determine the optimal gene transfection conditions, and detecting the expression of GM-CSF after transfection. The variation of GM-CSF gene-modified DCs were analyzed by morphological observation, phenotype analysis, and mixed lymphocyte reaction （MLR）. DCs were loaded with gastric cancer antigen obtained by frozen and thawed method. The stimulated DCs vaccination induced T lymphocytes, and the killing effect of T cells to gastric cancer cells was assayed by MTT. INF-γ production was determined with the INF-γ ELISA kit. Results： B220–CD11c＋ cells numbers increased after CCL3 injection. ELISA results showed that after GM-CSF gene modification, DC could produce high level of GM-CSF. When DCs were transferred AdGM-CSF gene at MOI equal to 1：100, GM-CSF level in culture supernatants reached saturation [（130.00 ± 12.61） pg/mL]. After GM-CSF gene-modification, DCs tended to more maturated through morphological observation and were phenotypically identical to typical DC and gained the capacity to stimulate allogeneic T cells. T lymphocytes stimulated with DC transduced with GM-CSF gene showed the specific killing effect on gastric carcinoma cells and produced high level of INF-γ [（1245.00 ± 13.75） pg/mL]. Conclusion： CCL3-recruited DCs modified by adenovirus-transducted GM-CSF could produce high level of GM-CSF, which tended to more maturated, and the capacity of activating allogeneic T lymphocytes proliferation was enhanced greatly. Moreover, they could stimulate specific cytotoxic T lymphocyte （CTL） to gastric cancer ex vivo.

EXPRESSION OF THE O^6－METHYLGUANINE－DNA METHYLTRANSFERASE GENE IN EIGHT HUMAN TUMOR CELL LINES

O6-methylguanine-DNA methyltransferase (MGMT) gene expression in 6 Mer+ (HeLa S3, SMMC-7721,SGC-7901, B-239, AGZY83-a, and Cc80 1) and 2 Mer- (SHG-44 , and HeLa MR) human tumor cell lines was examined. Southern blot analysis revealed no deletion, amplification, or rearrangement of the MGMT gene in these cell lines. However ,～ 1. 0 kb transcripts were detected in the 6 Mer+ cell lines but not in the 2 Mer-cell lines by Northern blot analysis. Furthermore,a rough correlation between MGMT activity and mRNA level in these cell lines was observed. These results suggest that transcriptional regulation of the MGMT gene is the molecular basis of the absence of MGMT activity in Mer-cell lines.

Effects of adenoviral-mediated gene transduction of NK4 on proliferation, movement, and invasion of human colonic LS174T cancer cells in vitro

AIM： To investigate the inhibitory effects of a recombinant adenovirus vector that expresses NK4, a truncated form of human hepatocyte growth factor （HGF）, on human colonic adenocarcinoma cells in vitro to establish a basis for future NK4 gene cancer therapy. METHODS： Cells from the LS174T human colonic adenocarcinoma cell line were infected with recombinant adenovirus rvAdCMV/NK4 and the effects of the manipulation on tumor cell proliferation, scatter, migration, and basement membrane invasion were assessed. Cells infected with a recombinant adenovirus vector （Ad-LacZ） expressing β-galactosidase served as the controls. RESULTS： We found that rvAdCMV/NK4 expression attenuated HGF-induced tumor cell scatter, migration, and basement membrane invasion （P 〈 0.05）, but did not inhibit tumor cell proliferation. CONCLUSION： HGF-induced LS174T tumor cell scatter, migration, and invasion can be antagonized by the recombinant NK4-expressing adenovirus.

Upreguiation of human telomerase reverse transcriptase mRNA expression by in vitro transfection of hepatitis B virus X gene into human hepatocarcinoma and cholangiocarcinoma cells

AIM： To study the changes of human telomerase reverse transcriptase （hTERT） mRNA expression in human hepatocarcinoma cell lines （HepG2） and cholangiocarcinoma cell lines （QBC939） after HBx gene transfection and to illustrate the significance of transcriptional regulation of hTERT gene by HBx gene in the carcinogenesis. METHODS： HepG2 and QBC939 cell lines were cultured and co-transfected with eukaryotic expression vector containing the HBx coding region and cloning vector containing enhanced green fluorescent protein （EGFP） coding sequence using lipid-mediated gene transduction technique. Thirty-six hours after transfection, EGFP expression in cells was used as the indicator of successful transfection. Flow cytometry was performed to determine the transfection efficiency. Cells were harvested and total RNA was extracted using TRIzol reagent. The expression of hTERT mRNA in HepG2 and QBC939 cell lines was assayed by reverse transcriptionpolymerase chain reaction. The expression of HBx protein in both cell lines was detected by immunocytochemical staining and Western blotting. RESULTS： Flow cytometry showed that the transfection efficiency was 46.4% in HepG2 cells and 29.6% in QBC939 cells for both HBx gene expression vector and blank vector. The expression of hTERT mRNA was meaningfully increased in HepG2 and QBC939 cell lines when transfected with HBx gene expression vector compared to those transfected with OPTI-MEM medium and blank vector. Immunocytochemical staining and Western blotting revealed HBx protein expression in HepG2 and QBC939 cells only when transfected with HBx gene. CONCLUSION： HBx gene transfection can upregulate the transcriptional expression of hTERT mRNA. The transactivation of hTERT gene by HBx gene is a newfound mechanism for pathogenesis of hepatocarcinomas and cholangiocarcinomas after HBV infection. 2005 The WJG Press and Elsevier Inc. All rights reserved

Expression of CD44v6 gene in normal human peripheral blood

AIM: To investigate if CD44v6 could be used as a molecular marker of cancer progression and metastasis through the detection of CD44v6 gene expression in normal human peripheral blood.METHODS: RNA was extracted from the peripheral blood mononuclear cells of 50 healthy donors, the expression of CD44v6 was investigated using reverse transcriptasepolymerase chain reaction (RT-PCR).RESULTS: CD44v6 mRNA was detected in 58% of healthy volunteers under the proper controls.CONCLUSION: Our results suggest that the measurement of CD44v6 expression in peripheral blood by RT-PCR is not suitable for detection of circulating tumor cells.

Adenovirus-mediated expression of pig α(1,3) galactosyltransferase reconstructs Gal α(1,3) Gal epitope on the surface of human tumor cells

Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.

Effect of NS398 on metastasis-associated gene expression in a human colon cancer cell line

AIM： To investigate the effect of NS398 on the metastasis-associated gene expression in LoVo colorectal cancer cells.METHODS： LoVo cells were treated with NS398 at the concentration of 100 IJmol/L for 24 and 48 h respectively. Total RNA was extracted with TRIzol reagents and reverse transcribed with Superscript Ⅱ and hybridized with cDNA mlcroarray （containing oncogenes, tumor suppressor genes, signal transduction molecules, adhesive molecules, growth factors, and ESTs） fabricated in our laboratory. After normalization, the ratio of gene expression of NS398 treated to untreated LoVo cells was either 2-fold up or 0.5-fold down was defined as the differentially expressed genes. Semi-quantitative RT-PCR was used to validate the microarray results.RESULTS： Among the 447 metastasis-associated genes, 9 genes were upregulated and 8 genes were downregulated in LoVo cells treated with NS398 for 24 h compared to untreated cells. While 31 genes were upregulated and 14 genes were downregulated in LoVo cells treated with NS398 for 48 h. IGFBP-5, PAI-2, JUN,REL, BRCA1, and BRCA2 might be the new targets of NS398 in treatment of colorectal cancer.CONCLUSION： NS398 might exert its anti-metastasis effect on colorectal cancer by affecting several metastasis-associated gene expression.

Polymorphism of glutathione S-transferase mu 1 and theta 1 genes and hepatocellular carcinoma in southern Guangxi, China

AIM: Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of a wide range of carcinogens, but deletions of the genes are commonly found in the population. The present study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: The genetic polymorphisms were studied at an aflatoxin highly contaminated region in Guangxi, China. Pdymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in blood samples. The case group was composed of 181 patients of HCC identified by the pathologists and the control group was composed of 360 adults without any tumor. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in the control were 47.8% and 42.7%, while those in the HCC group were 64.6% and 59.7%, respectively. The differences between HCC group and control group were very significant (P<0.01). GSTM1 and GSTT1 combined null genotypes in HCC group and control group were 38.2% and 18.5% respectively, and the difference was significant (P<0.05). CONCLUSION: The GSTM1 and GSTT1 null genotypes are associated with an increased risk of HCC in a special geographic environment. Combination of the two null genotypes in an individual is substantially increased twice the risk of HCC.

Enhanced chemosensitivity of p73α gene transferred into H1299 cell line of human lung adenocarcinoma

Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α plasmid was transferred into the cultured p53-null H1299 cells of human lung adenocarcinoma with the mediation of Dosper liposome; The cells resistant to G418 were selected. The expression of p73α gene in the cells was examined with Western blot. MTT assay was used to analyze the response of the transfected cells to cis-dichlorodiamine platinum (cDDP) and adriamycin (ADM). The rate of drug-induced apoptosis of the transfected cells was determined with flow cytometry and DNA fragmentation assay. The changes of the biological behaviors were observed with colony formation assay. Results: The transfected H1299 cells of human lung adenocarcinoma over-expressed p73α protein stably. MTT assay showed that the IC 50 values of cDDP and ADM were reduced by approximately 7 fold and 130 fold respectively in the transfected cells as compared with the untransfected ones. Lower concentration of the chemotherapeutic agents (1.25 μmol/L of cDDP and 0.05 μmol/L of ADM) could be employed to suppress markedly the growth of the transfected H1299 cells. The apoptotic rate induced by cDDP was increased from 10.1% to 38 4% (P<0.01) and that of ADM from 12.1% to 49.3% (P<0.01). The clonogenecity after the administration of chemotherapeutic agents was significantly lower in the transfected H1299 cells than in the parental cells (P<0.01). The sensitive enhancement ratios were 1.8 and 2.6 for cDDP and ADM respectively. Conclusion: The transfection of H1299 cells with wild type p73α gene results in an increase of the sensitivity of the cells to chemotherapeutic agents.

Effect of Cytokine on the Expression of Sodium Iodide Symporter Gene in Breast Cancer Cell

Objective: To investigate the effect of cytokines (TNF-α,IFN-γ and IL-6) on the expression of sodium-iodide symporter(NIS)gene in breast cancer cell(MCF-7). Methods:The breast cancer cell was cultureds with negative control culture or culture with different concentrations of cytokines for 72 h.NIS gene mRNA in breast cancer cells cultured was determined by reverse transcriptase-polymerase chain reaction(RT-PCR). Results:Expression of sodium-iodide symporter mRNA can be found decreasing along with increasing the concentration of cytokine dose-dependently. Conclusion: Cytokine may play a role in iodide-uptake modulating in breast cancer cells by their effect on NIS gene expression.

Adenovirus-mediated PTEN gene transfection suppresses growth and promotes chemosensitivity of endometrial carcinoma

Objective： To determine the potential of sustained transgene expression by intratumoral injection of Ad-PTEN in the nude mouse model of endometrial carcinoma. Methods and Results： We constructed recombinant adenovirus carrying the wild-type PTEN gene （Ad-PTEN）. RL95-2 cells, an endometrial carcinoma cell line lacking PTEN function, was infected with Ad-PTEN and showed increased expression of PTEN and chemosensitivity to doxorubicin, decreased proliferation rate, and elevated apoptosis and Go/G1 arrest. Furthermore, the tumorigenicity of these cells was also completely suppressed. These results indicated that gene therapy with Ad-PTEN could significantly inhibit the endometrial carcinoma xenografts growth in nude mice by intratumoral injection, induce apoptosis of tumor cells, and reduce expression of proliferating cell nuclear antigen （PCNA）. Immunohistochemistry analysis also showed that the expression of progesterone receptors （PR） in Ad-PTEN treated tumor cells were induced, while P-glycoproteins （P-gp） and estrogen receptors （ER） decreased significantly. Conclusion： PTEN may play an important role in the development of endometrial carcinoma. Our findings cast new lights for treatment ofendometrial carcinoma.