Anti-Tumor Effect of Curcumin on Human Cervical Carcinoma HeLa Cells In Vitro and In Vivo

Objective： To investigate the anti-tumor effect of curcumin on human cervical carcinoma HeLa cells in vitro and in vivo. Methods： （1） Human cervical carcinoma cell line HeLa was cultured in vitro. HeLa cells were treated with 5-50 μmol/L curcumin for 24. 48, 72 h and the growth inhibition rates of HeLa cells were measured by MTT method. Cell apoptosis was inspected by electron microscopy and flow cytometry （FCM）. （2） A transplanted tumor model by injecting HeLa cells into subcutaneous tissue of BABL/C mice was established and its growth curve was measured. 30 BABL/C mice with tumors were divided into 2 groups at random and 0.2 ml saline or 0.2 ml 250 μmol/L curcumin was injected into abdominal cavity respectively once everyday and lasted for ten days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. At last the expressions of caspase-3 and bax protein in transplanted tumors were detected by immunohistochemistry. Results： （1） Curcumin inhibited the proliferation of Lela cells on a dose-depending manner. Apoptosis of cells could be observed by FCM. Partial cells presented the characteristic morphological changes of apoptosis under electron microseope. （2） When 1×10^7 HeLa cells were inoculated for each mouse, 100% of the mice developed growing tumors after seven days. An inhibition effect was observed in treatment group, and the inhibition rate of curcumin was 74.33%. The expressions of caspase-3 and bax in the transplanted tumors were increased in curcumin group. Conclusion： Curcumin is effective as an anti-cancer drug not only in vitro but also in vivo.

EXPRESSION OF c-erbB-2 AND PCNA IN CERVICAL ADENOCARCINOMA AND ITS SIGNIFICATION

Objective: To investigate the significance of cerbB2 and PCNA expression in adenocarcinoma. Methods: Expression of cerbB2 and PCNA in 74 cases of adenocarcinoma of the uterine cervix was examined by immunohistochemistry. Results: The expression of cerbB2 was detected in 34 cases. The positive staining of cerbB2 was associated with increased lymph node metastasis (57.1% Vs 24.0%, P=0.041) and lower 5year survival rate (32.4% Vs 58.9%, P=0.008). The average PCNA labeling index (PCNA LI) was 40.6% (0.1% 91.4%). High PCNA LI was associated with lymph node metastasis (56.4% Vs 38.5%, P=0.016) and lower 5year survival rate (28.7% Vs 64.4%, P=0.005). Positive staining of cerbB2 were associated with high PCNA LI (44.7% Vs 34.6% P=0.003). Conclusions: cerbB2 and PCNA LI were associated with malignant biological behavior and poor prognosis of patients with cervical adenocarcinoma.

ANTITUMOR EFFECTS OF POLYETHYLENE GLYCOLMODIFIED RECOMBINANT HUMAN INTERLEUKIN-2 ON MOUSE UTERINE CERVICAL CARCINOMA IN VIVO

Polyethylene glycol (PEG-8000)-modified recombinant human interleukin-2 (PEG-rIL-2) is a cytokine with prolonged circulatory half-life. In this paper, the antitumor effects of PEG-afL-2 against mouse uterine cervical carcinoma (U14) transplanted intraperitoneally or subcutaneously is reported. PEG-rIL-2 at different doses was administered intraperitoneally. The results showed that PEG-rIL-2 (4500 IU, i.p., QD5) prolonged survival time of mice bearing ascites tumor as compared to rIL-2 (P<0.01), but PEG-rIL-2 at lower doses was without therapeutic effect. In addition, compared to rIL-2, PEG-rIL-2 at different doses (1500-13500 IU, s.c.,QD5) caused significant dose-dependent growth inhibition of solid tumor (P<0.01) when the treatment started at day 4 after subcutaneous inoculation of tumor.

PROGNOSTIC FACTORS AFFECTING THE RESULTS OF SURGICAL TREATMENT OF CERVICAL CANCER

From October, 1963 to December, 1992, 1213 cases with cervical cancer were treated surgically in our hospital, among whom 922 cases, including 305 in stage 0,123 in stage IA, 212 in stage IB, 265 in stage IIA, 17 in stage IIB, were operated before February, 1990. Among the 617 available cases, excluding those in stage 0, the five-year survival rates 95.1 % in stage IA, 91.0% in stage IB, 83.1 % in stage IIA, and 59.0% in stage IIB, respectively. The results showed that cervical tumor greater than 4 cm in diameter, invasion in muscular layers, lower degree of differentiation and pelvic lymph nodes metastasis would lead to worse therapeutic effects. The method of pelvic lymphadenectomy, pathological types, and ages of the patients, however, did not at all correlate with the survival rates of the patients. For those who have risk factors mentioned above active adjutant treatments are indicated.

Telomerase activity in cervical intraepithelial neoplasia

Background It was reported that telomerase expression is closely associated with cellular immortality and cancer. This study was designed to investigate the relationship between telomerase expression and the carcinogenesis of cervical cancer, the possible use of telomerase as a marker of cervical intraepithelial neoplasia (CIN) progression or regression, and the natural history of CIN.Methods Telomeric repeat amplification protocol (TRAP) assay was used to measure telomerase activity in cervical scrapings and biopsy samples obtained from 105 cases affected with various cervical conditions, including chronic cervicitis (n =20), CIN (n =64, 16 cases of CIN Ⅰ , 20 cases of CIN Ⅱ , and 28 cases of CIN Ⅲ), and invasive squamous cell carcinoma (n =21).Results In exfoliated cell samples, telomerase activity was detected in 5 of 20 (25. 0%) cases of cervicitis, 10 of 16 (62. 5%) cases of CIN Ⅰ , 11 of 20 (55. 0%) cases of CIN Ⅱ , 23 of 28 (82.1%) cases of CIN Ⅲ, and 13 of 21 (61. 9%) cases of carcinoma. In cervical biopsy samples, telomerase activity was detected in 6 of 20 (30. 0%) cases of cervicitis, 8 of 16 (50. 0%) cases of CIN Ⅰ , 9 of 20 (45. 0%) cases of CIN Ⅱ , 27 of 28 (96. 4%) cases of CIN Ⅲ, and 20 of 21 (95. 2%) cases of carcinoma. Telomerase activation was significantly higher in CIN samples than in cervicitis samples. Telomerase activity was detected at similar frequency in samples from cervical scrapings and cervical biopsies.Conclusion These results seem to suggest that telomerase expression may be associated with carcinogenesis of the cervix. TRAP assay of cervical scraping samples could be used to monitor and predict the development of CIN in clinical practice.