肝细胞癌组织中庚型肝炎病毒感染的研究

目的为了探讨庚型肝炎病毒（HGV）在肝细胞癌（HCC）组织中存在状态．方法选自我院尸解的原发性肝癌病例53例，其中男49例，女4例，平均年龄56．2（22～77）岁，经血清学检测，有HBV感染41例，HCV感染2例，HBV＋HCV感染2例，两者均阴性8例，甲醛固定肝组织，石蜡包埋，采用抗HGVNS5单克隆抗体以免疫组化进行检测，DAB显色．并设立阴性及阳性对照．结果统计采用卡方检验方法．结果本组病例中，HGAg检出率37．7％（20／53），HG抗原（HGAg）主要存在于肝细胞或肝癌细胞胞质内呈细颗状分布．在癌旁组织中，HGAg阳性细胞多弥漫或呈片状分布在肝小叶内及假小叶周边．在癌组织中则多散在或呈灶性分布，但HGAg表达强度低于癌旁组织．在非乙非丙、乙、丙型肝炎病毒组中，分别检出HGAg2／8例（25％），16／41例（39％）和2／2例，在乙＋丙型组2例中HGAg均为阴性．HGV感染组与未感染组从有无肝炎病史及其时间上无明显差别，但从多次大量输入血液制品史上有差异，P＜0．05．结论本组病例经免疫组化检测，HCC患者中有较高HGV感率、但从临床资料看，HGV感染组与未感染组从有无肝病史及其时间上无明显差异，似提示HGV感染与HCC发生没有关系．本研究中HBV，HCV重叠HGV感染率较高．HGV感染与多次大量输用血液制品密切相?

肝细胞凋亡与肝癌癌前病变

目的观察肝细胞癌（HCC）癌分组织与单纯肝硬变二者在肝细胞凋亡的区别，以探讨癌前病变的特性．方法HCC癌旁标本及单纯肝硬变标本分别为24及对例（A及B组），全部作原位末端标记（ISEL），HBsAg免疫组化及HE观察分析ISEL阳性强度分4级，作A、B组比较，卡方统计．结果A组的肝细胞ISEL阳性率及阳性强度均显著高于B组（P＜0．01）．阳性细胞核深棕色，散在分布，以汇管区及纤维隔周边部为多．A组绝大多数属静息性门脉性肝硬变；而B组尚有慢活肝及侵重肝肝硬变炎症B组较A组明显（P＜0．05）．HBsAg阳性率A组89．4％，B组93．7％ISEL阳性与HBsAg、肝细胞活跃增生和肝细胞非典型增生无相关性此外，发现A组中有1例“凋亡性肝硬变”，其ISEL及HE均证明50％的肝细胞有凋亡结论HCC癌旁肝硬变的凋亡发生率明显高于单纯肝硬变者，认为肝细胞凋亡是HCC癌前病变的一种特性，与癌的发生有关．

Contrast-enhanced ultrasound for predicting differentiation degree of hepatocellular carcinoma

Objective To explore the value of contrast-enhanced ultrasound(CEUS)for predicting differentiation degree of hepatocellular carcinoma(HCC).Methods Totally 86 HCC patients confirmed by postoperative pathology were retrospectively enrolled and divided into poorly differentiated,moderately differentiated and highly differentiated groups according to postoperative Edmondson-Steiner grading.Preoperative CEUS parameters were compared among groups,and binary logistic regression was used to analyze CEUS-related independent predictors of HCC with different differentiation.The receiver operating characteristic curves of parameters being significant different among groups were drawn,the areas under the curve(AUC)were calculated,and the efficacy for predicting HCC with different differentiation degree was evaluated.Results There were 29 cases in poorly differentiated group,37 in moderately differentiated group and 20 cases in highly differentiated group.The arrival time of contrast agent in poorly differentiated group was earlier than that in moderately and high differentiated groups(both P<0.05),while in moderately differentiated group was not significantly different with that in highly differentiated group(P>0.05).The washout grade were significantly different between each 2 groups(all P<0.05).The arrival time of contrast agent and washout grade were independent predictors of highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC,and washout grade also was independent predictor of highly or moderately differentiated HCC(all P<0.05).The AUC of the arrival time of contrast agent for predicting highly or moderately differentiated,highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC was 0.615,0.787,0.690 and 0.724,respectively,while of washout grade was 0.801,0.927,0.795 and 0.841,respectively.Conclusion CEUS could be used to effectively predict differentiation degree of HCC.

应用激光捕获显微切割技术对肝细胞癌8号染色体短臂杂合性缺失的研究

目的探讨8p杂合性缺失(LOH)的特点及其与肝细胞癌(HCC)临床病理特征的相关性。方法选择8p上5个具有高度多态性的微卫星标记。对62例HCC组织利用激光捕获显微切割(LCM)技术进行LOH分析。结果有56．5％(35／62)的HCC患者在1个或多个基因位点发生LOH。LOH频率最高的3个位点依次为D8S298(51．1％,24／47)、DSS1771(48．8％,21／43)和 D8S264(43．5％,20／46)。D8S298位点肝内转移者的LOH频率明显高于无转移者(尸<0．05);在 DSS1771位点,肿瘤直径>3 cm的LOH频率明显高于≤3 cm组(P<0．05)。结论HCC在染色体 8p特定位点上LOH明显,在这些区域可能存在一个或多个与HCC发生发展相关的肿瘤抑制基因。8p上部分位点的LOH与临床病理特征有一定的相关性。

肝癌及癌旁组织中端粒酶检测的临床意义

目的研究端粒酶作为原发性肝细胞癌（ＨＣＣ）肿瘤标志物的可能性。方法采用ＴＲＡＰ方法检测了３３例原发性肝细胞癌及其３３例癌旁组织、４例肝转移癌及其４例癌旁组织、６例肝良性肿瘤和６例正常肝组织中的端粒酶活性。结果３３例原发性肝细胞癌组织中，有３０例端粒酶表达阳性，其阳性率为９０．９％。３３例癌旁组织中，有９例端粒酶表达阳性，其阳性率为２７．３％。４例肝转移癌端粒酶活性均阳性，４例癌旁组织中，２例端粒酶表达阳性。６例肝良性肿瘤中，仅１例端粒酶表达阳性。６例正常肝组织端粒酶表达均阴性。肝癌组织端粒酶表达与肿瘤临床病理特征无关。结论肝癌组织中普遍存在端粒酶活性表达，而良性和正常肝组织中端粒酶活性较少表达。

Regulation of Bcl-2 Family in TIP30-Induced Apoptosis in Hepatoblastoma Cells

Objective: To investigate the role of TIP30 in the apoptotic signal pathwayin HepG2, and Hep3B and Hu-7 hepatoblastoma cell lines. Methods: In order to confirm whether TIP30conducted Bcl-2 family was involved in apoptosis signal pathway, MTT assay, in situ 3' end labellingof DNA assay and Western blot were carried out to detect the diverse apoptotic function of TIP30and the regulation of Bcl-2 family. Results: TIP30 induced apoptosis as evidenced by morphologicalchanges in hepatoblastoma cells, which was accompanied by up-regulating Bax and Bad proteins andstimulating them from cytoplasm to mitochondria, and down-regulating Bcl-xl, while it had no effecton the level of Bak protein. Conclusion: TIP30 induced apoptosis partly by modulating the proteinlevels of members of Bcl-2 family in hepatoblastoma cells. Elucidating the mechanism by which TIP30induces cell death might establish it as an anticancer factor.

Apoptosis of Human Hepatoma Cells Induced by Gynostemma Pentaphyllum Makino

Objective： To identify the proapoptotic effects of Gynostemma pentaphyllum Makino （GpM） on human hepatoma cells. Methods： The effects of GpM on the cell apoptosis of human hepatoma cell line Huh-7 was assessed by flow cytomety. The expression of Bcl-2, Bcl-XL, Bax and Bad molecules in hepatoma cells treated with GpM was detected by Western blot. Results： After treatment with 20 mg/mL GpM for 24 h, 56% of Huh-7 cells were undergoing apoptosis, while cell death was only observed in 12% of humaa fibroblast cells treated with GpM. Western blot demonstrated that, Bcl-2 was markedly decreased in Huh-7 cells treated with GpM. Whereas, Bax was significantly up-regulated in Huh-7 cells treated with GpM. Conclusion： Treatment of human hepatoma cells with GpM induced apoptosis through the down-regulation of Bcl-2, and up-regulation of Bax.

High Rate of P16 Methylation Associated with Hepatitis B Virus Infection in Hepatocellular Carcinoma

Objective： To investigate the potential linkage between high rate of p16 methylation and hepatitis B virus （HBV） infection, methylation status of p16, HBV infection markers in serum and HBV-DNA replication level in cancerous and non-cancerous tissue of 32 cases of hepatocellular carcinomas （HCC） with HBV infection and 12 HCCs without HBV infection were examined. Methods： p16 methylation was detected with methylation-specific polymerase Chain reaction （PCR）, and HBV markers were examined with real-time PCR and immunologic method. Results： Methylation of p16 promoter was found in 31 （70.5%） of 44 cancerous tissues of HCC, 2 （16.7%） of 12 HCC without HBV infection, 29 （90.6%） of 32 HCCs with HBV infection marker, p16 methylation was detected in 5 （83.3%） of 6 HCCs positive for HBsAg and HBeAg, 17 （94.4%） of 18 HCCs positive for HBsAg and negative for HBeAg, 7/8 （87.5%） of HCCs positive for other HBV infection markers, such as HBsAB, HBcAb, HBeAb. p16 methylation products were also found in non-cancerous tissues of 4 cases of HCCs with HBV infection, not detected in non-cancerous tissues without HBV infection. HBV-DNA was detected in cancerous tissues of 29/32 （90%） HCCs with HBV infection. Surprisingly, Methylation product of p16 promoter was found in all cases （29/29） of HCCs with detectable HBV-DNA in neoplastic tissue. Conclusion： Persistent HBV infection may promote p16 hypermethylation, suggesting that HBV, via enhancing the aberrant methylation of p16, indirectly involved in development of HCC.

A Novel Replication-competent Adenovirus CNHK500 in the Treatment of Heptocellular Carcinoma In Vitro

Objective: To evaluate the therapeutic efficacy of replicative adenovirus CNHK500 in the treatment of hepatocellular carcinoma. Methods: Virus proliferation assay, cell viability assay and Western blot were performed to assess the selective replication and cytolysis of CNHK500 in telomerase positive liver cancer cells Hep3B, HepGII, SMMC7721 and in normal cells. Results: The replicative multiples of CNHK500 in HepGII, Hep3B and SMMC7221 after 96 h of virus proliferation were 52 000, 396 984.9 and 632 911.3 fold respectively, similar to those of wtAd5. However, CNHK500 demonstrated more significant attenuated replicative ability in normal cell lines than wtAd5. CNHK500 replicated only 3.1-100 fold at 96 h, while the wtAd5 still reached 3160-17 357 fold. CNHK500 could cause half of HepGII cells death within 7 days at MOI 2, in Hep3B cell lines the IC50 was as low as MOI 0.01, whereas the IC50 in BJ cell was as high as MOI 1000. CNHK500 E1A protein could only be detected in hepatocellular cancer cells but not in normal cells under normoxia. E1B protein could only be detected under hypoxia condition at a MOI of 1. Conclusion: CNHK500 can efficiently replicate in and kill liver cancer cells as well as wtAd5 do while it is severely attenuated in proliferation and cytolysis among normal cells. It would be a prominsing strategy for liver cancer tratment.

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

Objective： To observe the recurrence and prognosis of hepatocellular carcinoma （HCC） patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 （Tα1） postoperatively. Methods： From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups： control group （n=35） received hepatectomy only; treatment group （n=35） received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results： In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% （P=0.0000）; HBeAg seroconverted rate was 73.0% vs. 7.5% （P〈0.05）; the recurrent rate was 10.0 vs 6.5 months （P=0.0032）; the median survival time was 12.5 vs. 6.0 months （P=0.0023）, respectively. Conclusion： Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication.

Expression of Lung Resistance Protein （LRP） Gene in Hepatocellular Carcinoma and Its Significance

Objective: To study the multidrug resistance (MDR) mechanism of lung resistance protein (LRP) gene in hepatocellular carcinoma (HCC), and the relations among the expression of the LRP gene and clinicopathologic features, the influence of α-fetoprotein (AFP), and prognosis of patients who received adjuvant chemotherapy after resection of HCC. Methods: The expression of the LRP gene encoding LRP and mRNA LRP was detected in tissues from 54 untreated patients with HCC, adjacent tissues from 24 patients with HCC and archival paraffin-embedded tissues from 12 patients with posthepatitic cirrhosis. The relationship between the LRP gene expression and the change of AFP level was analyzed in the 24 postoperative HCC patients whose AFP was measured after 2 weeks. All of the HCC patients were followed up. Results: The percentage of positive expression of LRP and mRNA LRP in the 3 tissues was 61.1%, 33.3%, 16.7%, and 75.9%, 37.5%, 33.3% respectively. There was significant difference between the untreated HCC tissue and other tissues (P<0.05). No difference existed between the LRP gene expression and clinicopathologic findings, age, sex, and tumor size (P>0.05), but the expression was related to the degree of differentiation of HCC (P<0.05). The effective rate of AFP in the LRP gene positive expression group or in postoperative chemotherapeutic patients was very lower than that in the negative group (P<0.05). Although the mean survival time of postoperative HCC patients in negative LRP gene expression group was longer than that of positive group, there was no difference between them (P<0.05). Conclusion: LRP gene expression is related to MDR of HCC and initiates the intrinsic MDR. Detection of LRP gene expression is of great guiding significance in accessing chemotherapeutic resistance of HCC. As an index to chemotherapy of HCC, detection of LRP expression provides evidence for making individual chemotherapeutic treatment,and reversing MDR in HCC. Although LRP gene expression correlates with the tumor differential degree (P<0.05), it perhaps does not relate with the prognosis of HCC patients.

Expression Profiles of TRAIL Receptors and Their Clinical Significance in Human Hepatocellular Carcinoma

Objective To investigate the expression profiles and their clinical significance of TRAIL receptors (TRAILR) in human hepatocellular carcinoma (HCC). Methods The expression profiles of TRAILR were determined in 60 samples from hepatocellular carcinoma, 20 from normal liver tissue and two HCC cell lines HepG2, SMMC-7721 by in situ hybridization. Results Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples (higher DR expression level and lower DcR expression level) were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. The expression level of DR was correlated with HCC differentiation and stage. The weaker expression was more commonly found in HCC with poor differentiation and late stage, while the stronger expression was more common in HCC with middle to high-differentiation and early stage. No relationship was found between DR and gender, age, negative or positive HBsAg, tumor size, grade or metastasis. Multidrug resistance cell lines expressed lower level DR. Conclusion TRAILR expression was prevalent and discrepancy of receptor types was exited in HCC. Loss of DcR1 may contribute for TRAIL therapy for HCC. Key words TRAILR - apoptosis - hepatocellular carcinoma Supported by the Major Fundation of Ministry of Health, NO. 2001–2003

mRNA Expression of the Cancer-testis Antigens SSX1 and SSX4 in Human Hepatocellular Carcinomas

Objective: To detect the mRNA expression of the cancer-testis antigens (CT) SSX1 and SSX4 gene in human hepatocellular carcinomas (HCCs) and to investigate the specificity of their expression in HCCs. Methods: The mRNA expression of SSX1 and SSX4 in HCC tissues and the corresponding nearby liver tissues in 35 cases was detected by using RT-PCR; Six positive RT-PCR products were randomly selected and sequenced. Results: In all 35 HCC tissues, SSX1 in 27 cases (81%) and SSX4 in 23 cases (73%) were detected, and their expression was negative in the liver tissues nearby HCC and the non-tumor liver tissues (12 cirrhotic tissues and 15 normal tissues). In all 6 cases selected randomly, the results of DNA sequencing were identical with the cDNA sequence of SSX1 and SSX4 genes. The SSX1, SSX4 mRNA expression was not significantly correlated with age, sex, the tumor size, the level of tumor differentiation, the serum AFP level and the infection rate of HBV and HCV respectively (P>0.05). Conclusion: The SSX1, SSX4 mRNA expression was greatly specific in HCCs, which would not only provide the ideal target molecular sites for HCC tumor vaccines, but also establish the potential value of the polyvalent tumor-antigen vaccines for HCC therapy and its theory bases.

Histopathological study of hepatocellular carcinoma after transcatheter hepatic arterial embolization

AIMS To study the histopathological changes in hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS Histopathological analysis was made in 39 cases of liver neoplasms after TAE and 11 cases of liver neoplasms after digital selective angiography (DSA), including pathological type, histological grade, necrotic degree, capsule, times of treatment, injured vessel and lymphocyte infiltration. RESULTS Six cases with 100% necrosis, 14 cases with 30% 95% necrosis, 19 cases with 0% 5% necrosis after TAE and 11 cases without necrosis after DSA were found histologically. The necrosis was related to the pathological type, capsule, injured vessels, but not to the histological grade, time of treatment and lymphocyte infiltration of the liver neoplasms. CONCLUSIONS TAE is an effective therapy for the late stage HCC. The encapsulated HCC is a preferable indicator for TAE.

Microsatellite Alterations on Chromosome 8 of Hepatocellular Carcinoma

Objective: To study the features of microsatellite alterations on chromosome 8 and their asso- ciation with clinicopathological characteristics of hepatocellular carcinoma (HCC). Methods: Ten highly- polymorphic microsatellite markers on chromosome 8 were selected to be detected for loss of heterozygosity (LOH), microsatellite instability (MSI) and allelic imbalance (AI) in 56 HCC using MegaBACE 500 auto- matic DNA analysis system. Results: LOH was found in 37 of 56 HCC (66.1%) on at least 1 locus, and the top three loci were D8S261(53.5%), D8S1721(52.5%) and D8S1771(52.5%). LOH frequency on D8S277 was signi?cantly higher in cases positive for serum HBsAg than in those negative for HBsAg (P <0.01). Similarly, LOH on D8S261, D8S298 and D8S1733 occurred more frequently in patients with negative HB- sAg than those with positive HBsAg (P <0.01). LOH on D8S298 and D8S1771 was more frequent in those tumors larger than 3 cm in size (P <0.05 or P <0.01). LOH frequencies of D8S1721 were signi?cantly higher in the patients with absent or not intact tumor capsule than in those with intact tumor capsule (P <0.05). LOH on D8S298 and D8S1771 was more frequently detected in tumors with intrahepatic metastasis than in those without intrahepatic metastasis (P <0.01). MSI was found in 12.5% (7/56) cases, and AI was found in 19.6% (11/56), no correlation was found between MSI and AI and clinicopathological character- istics of HCC. Conclusion: Frequent microsatellite alterations on chromosome 8 existed in HCC. LOH, which represents tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis; MSI representing mismatch repair gene pathway ranks next. LOH at a particula locus is associated with the clinicopathological parameters of human HCC.

Bacterial infections in cirrhotic patients with hepatocellular carcinoma

AIMS To establish the prevalence of bacterial infection in cir- rhotic patients with hepatocellular carcinoma(HCC). METHODS All 719 cirrhotic patients with HCC were investigat- ed retrospectively for the prevalence of bacterial infections. RESULTS The incidence of bacterial infection was 15.4% (111/719).According to Child-Pugh classification,the inci- dences of bacterial infection in class A,B and C were 2.3%,8. 0%,and 26.4 %,respectively.The bacterial infection increased with the severity of cirrhosis and severe bacterial infections usual- ly occurred in Child-Pugh class B and C patients. CONCLUSIONS The susceptibility of HCC patients to bacterial infection is mainly due to the underlying cirrhosis and not to the HCC itself.

Activity Determination of 8 Chinese Herbs against Hepatoma Cell SMMC-7721 in Vitro by MTT Method

[Objective] The aim was to build up a set of efficient and rapid models for laboratory to screen anti-hepatocellular carcinoma active substance in vitro. [ Method] By using MTT method, the activities of anti-hepatocellular carcinoma SMMC-7721 in vitro from Cymbopogon distans, Lobelia chinensis, Buddleja offlcinalis, Glycyrrhiza uralensis, Sanguisorba officinalis, Bupleurum chinense, Apium graveolen and Curuma zedoaria were tested. The growth curve of hepatoma cell was described, and the growth status in different periods were observed by inverted microscope. [ Result] Cells induced by active substance would be condensing, clear brim, which have significant differences from normal SMMC- 7721 cells. The results suggested that ESCG, ESCC, ESCB could inhibit proliferation of SMMC-7721 cells at the concentration of 1.0 -1.5 mg/ml, and the inhibition rate were 51.6%, 48.5%, 52.9% respectively. With the increasing of concentration, the inhibition strengthened. [ Conclusion] MTT method could be used as a basic model for screening important anti-hepatoma.

Quantitative Detection of Osteopontin High Expression in Human and Rat Hepatocellular Carcinoma

Objective： Osteopontin （OPN） is a secreted phosphorylated glycoprotein that is implicated in proliferation and migration of several malignancies including hepatocellular carcinoma （HCC）. In pregent study, human HCC specimens were collected and rat HCC model was chemical-induced to elucidate the expression significance of OPN in HCC progression. Methods： OPN expression was detected quantitatively by real-time reverse transcription polymerase chain reaction （RT-PCR）. Male Sprague-Dawley rats were administrated diethylnitrosamine （DENA） to induce HCC and OPN expression was dynamically assessed. Results： In 69 cases of 103 HCC patients （67%） OPN was highexpressed in HCC tissues than that in adjacent non-tumor liver tissues and in 58 cases of these 69 cases more than 2-fold. OPN expression was significantly different between HCC and adjacent liver tissues （0.53±0.91 vs 0.11±0.28, P〈0.001）. OPN expression was gradually elevated in occurrence and development of rat HCC. Conclusion： OPN was highexpressed in human HCC and gradually elevated in rat HCC progression.

Role of Hypoxia-inducible Factor-1α in Formation of Muttidrug Resistance Induced by Microenvironment in Hepatocellular Carcinoma

Objective： To explore the role of hypoxia-inducible factor-1α （HIF-1α） in formation of multidrug resistance （MDR） induced by microenvironment and to find a new and effective molecular target on preventing and reversing chemoresistance in hepatocellular carcinoma （HCC）. Methods： In HepG2 cells exposed to hypoxia, low glucose or transfected by plasmid pcDNA3/HBX, the expression of HIF-1α mRNA and protein was respectively detected using real-time fluorescent quantitative PCR and Westernblot technique and its expression localization was investigated by immunocytochemical technique. Plasmid pcDNA3/HIF-1α was transfected into HepG2 cells and then the expression of multidrug resistance related genes mdrl, multidrug resistance-associated protein 1 （MRP1） and lung resistance protein （LRP） in transfected cells was determined by the same methods. Results： In HepG2 cells respectively exposed to hypoxia, low glucose or transfected by plasmid pcDNA3/HBX, HIF-1α was overexpressed at mRNA and protein levels to varying degrees and translocated into nucleus. The gene expression levels of mdrl, MRP1 and LRP in HepG2 cells transfected by plasmid pcDNA3/HIF-1α were respectively increased by 2.4±0.2, 2.2±0.3 and 2.3±0.4 folds as compared with those in non-transfected HepG2 cells （all P〈0.01） and similar changes were observed in protein level. Conclusion： Microenvironmental factors around HCC could modulate the transcription of the MDR related genes by nuclear transcript factor HIF-1α, thereby conferred MDR of HCC. Up-regulation of HIF-1α expression could hold a central position in the formation of MDR of HCC induced by microenvironment. HIF-1α probably becomes a new and effective molecular target on preventing and reversing MDR in HCC.