Effect of long-chain non-coding RNA TUG1 on radiosensitivity of human cervical cancer XB1702 cells by adsorption of miR-145 / 中华放射肿瘤学杂志

Objective@#To evaluate the effect of long-chain non-coding RNA TUG1 on the radiosensitivity of cervical cancer cells and explore its underlying mechanism.@*Methods@#The expression of TUG1 and miR-145 in cervical cancer cells XB1702 and normal endometrial stromal cells (ESCs) was detected by qRT-PCR. The transfected si-NC, transfected si-TUG1, transfected si-NC combined with irradiation, transfected si-TUG1 combined with irradiation, si-TUG1 and anti-miR-NC co-transfected and, si-TUG1 and anti-miR-145 co-transfected groups were established, which were transfected into XB1702 cells by liposome method. The survival fraction of each group was detected by colony formation assay. The cell apoptosis of each group was detected by flow cytometry. The fluorescence activity of each group was assessed by dual luciferase reporter gene assay.@*Results@#Compared with the normal ESCs, the expression of TUG1 was significantly up-regulated, whereas that of miR-145 was significantly down-regulated in the cervical cancer cells XB1702. Silencing TUG1 significantly increased the survival fraction of XB1702 cells, promoted cell apoptosis and enhanced the radiosensitivity of irradiation to XB1702 cells. TUG1 could target and regulate the expression of miR-145. Suppressing miR-145 reversed the silencing effect of TUG1 on inhibiting proliferation, accelerating apoptosis promotion and enhancing sensitization of XB1702 cells.@*Conclusions@#Silencing long-chain non-coding RNA TUG1 can enhance the radiosensitivity of cervical cancer cells. The mechanism may be related to targeting miR-145, which will provide a target for radiotherapy of cervical cancer.

Effect of hypoxia on epithelial growth factor receptor expression and cell apoptosis of breast cancer and cervical cancer xenografts in nude mice / 中华放射肿瘤学杂志

Objective To observe the effect of hypoxia on the expression of epithelial growth factor receptor (EGFR) and cell apoptosis of breast and cervical cancer xenografts in nude mouse models.Methods The nude mouse models with MCF-7 and HeLa xenografts were established.The degree of hypoxia and EGFR expression were observed by confocal microscopy.The influence of EGFR expression on cell apoptosis under hypoxia was observed by TUNEL assay.Results EGFR expression was either up-regulated or down-regulated in the MCF-7 and HeLa cells with high degree of hypoxia.Furthermore,the degree of apoptosis was reduced in tumor tissues with high EGFR expression compared with that in those with low expression of EGFR.Conclusion The hypoxia in MCF-7 and HeLa cells exerts heterogeneous effect on EGFR expression.Under hypoxic conditions,EGFR exoression is negatively correlated with cell apoptosis.

A study on the application of povidone - iodine diluent in intraoperative nursing of cervical cancer surgery / 预防医学

Objective To investigate the effect of povidone - iodine diluent on proliferation and apoptosis of cervical cancer cell HeLa and to provide the theoretical basis for its clinical application. Methods Human cervical cancer cell line HeLa in logarithmic growth phase were treated with different dilutions of povidone - iodine and the cells treated with physiological saline were set as the control group. The cells viability,morphological change,formation of apoptotic bodies,cell apoptosis and the apoptosis - related protein expression in HeLa cells were assessed by MTT assay,Hoechst33342 staining, AnnexinV / PI flow cytometry and Western blotting. Results Povidone - iodine diluent remarkably inhibited human cervical cancer cell line HeLa growth in a concentration - dependent manner. The inhibitory rates of HeLa cells were 25. 3% , 30. 8% ,33. 4% ,60. 3% ,71. 2% ,85. 3% ,89. 1% and 91. 2% when the concentration of povidone - iodine solution were 0. 001% ,0. 005% ,0. 01% ,0. 05% ,0. 1% ,0. 5% ,1% and 2% ,respectively. The nuclear chromatin of HeLa cells treated with povidone - iodine dilution was agglutinated and contracted,and the nucleus was fragile and appeared apoptotic body,with dense and dense stain or fragment dense staining. With the increase of the concentration of povidone -iodine dilution,the apoptotic rate of HeLa cells increased,so were Caspase - 8 ,Caspase - 3 and cleaved PARP. Conclusion Diluted povidone - iodine can strongly inhibit the proliferation of human cervical cancer cell line HeLa and the possible mechanism was the promotion of apoptosis.

Effects of Src on cervical cancer cells proliferation and apoptosis through ERK signal transduction pathway / 中华流行病学杂志

Objective To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway.Methods Experimental study was carried out in vitro.Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2.Then,the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM).Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2,c-Fos and c-Jun mRNA and protein respectively.The database was established and analyzed with SPSS statistical software (version 20.0).Results After down-regulating Src,the cell proliferation was inhibited and cell apoptosis was induced.The proportions of G0/G 1 stage of Hela and C33A cell in cell cycle increased while G2/M and S stages decreased.Meanwhile,the mRNA levels of ERK 1,ERK 2,c-Fos and c-Jun increased.And the expression levels of ERK 1/2,phosphorylated ERK 1/2 (p-ERK 1/2)and phosphorylated c-Fos (p-c-Fos) protein decreased,while c-Jun and phosphorylated c-Jun (p-c-Jun)protein expression increased.In addtion,the change level of Hela cell,p-ERK 1/2 and c-Fos protein were lower than that of C33A cell before and after the Src inhibition.Conclusions Src,involved in regulating the expression of key factors of the ERK signal transduction pathway including p-ERK 1/2 and p-c-Fos,might be capable of promoting the proliferation of cervical cancer cells and inhibiting their apoptosis.The infection with HPV might have adjustable effect on this process.

Effects of Src on cervical cancer cells proliferation and apoptosis through ERK signal transduction pathway / 中华流行病学杂志

Objective To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway.Methods Experimental study was carried out in vitro.Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2.Then,the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM).Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2,c-Fos and c-Jun mRNA and protein respectively.The database was established and analyzed with SPSS statistical software (version 20.0).Results After down-regulating Src,the cell proliferation was inhibited and cell apoptosis was induced.The proportions of G0/G 1 stage of Hela and C33A cell in cell cycle increased while G2/M and S stages decreased.Meanwhile,the mRNA levels of ERK 1,ERK 2,c-Fos and c-Jun increased.And the expression levels of ERK 1/2,phosphorylated ERK 1/2 (p-ERK 1/2)and phosphorylated c-Fos (p-c-Fos) protein decreased,while c-Jun and phosphorylated c-Jun (p-c-Jun)protein expression increased.In addtion,the change level of Hela cell,p-ERK 1/2 and c-Fos protein were lower than that of C33A cell before and after the Src inhibition.Conclusions Src,involved in regulating the expression of key factors of the ERK signal transduction pathway including p-ERK 1/2 and p-c-Fos,might be capable of promoting the proliferation of cervical cancer cells and inhibiting their apoptosis.The infection with HPV might have adjustable effect on this process.

Correlation between RRM2 Expression Level of Cervical Cancer Cell Line Siha and C33a and Cell Sensi-tivity to Gemcitabine / 中国药房

OBJECTIVE:To study the correlation between RRM2 expression of cervical cancer cell line C33a and Siha and cell sensitivity to gemcitabine(Gem). METHODS:C33a and Siha were treated with 0.1-3.2 μmol/L and 0.5-512 μmol/L of gemcitabine respectively for 72 h;cell viability was measured by MTT assay to calculate the value of IC50. The expression of RRM2 was mea-sured by Western blot and RT-PCR. Siha cell was treated with gradient concentration and large dose of Gem to establish Siha/Gem drug-resistant cell line. RNA interference technology knockdown the expression of RRM2 in Siha/Gem cell,and IC50 of Gem to cell was determined before and after knockdown. RESULTS:The IC50 values of Gem to Siha and C33a were 16.8 μmol/L and 0.63μmol/L. Compared with C33a cells,the expression of RRM2 in Siha cell was higher. Compared with Siha cells,Siha/Gem drug-re-sistant cell(drug resistant index of 16.26)showed higher RRM2 expression. Siha/Gem drug-resistant cell knockdown RRM2,IC50 of Gem to it was decreased,and inverse drug resistant times was 4.24. CONCLUSIONS:There is an negative correlation between RRM2 expression and Gem sensitivity in cervical cancer cell lines. The knockdown of RRM2 in Siha/Gem increases the sensitivity to Gem.

Demethylation of RARβ2 Gene Promoter by Withania somnifera in HeLa Cell Line.

An important molecular target for cancer therapy is the possible reactivation of tumor suppressor genes that have been silenced by promoter methylation. It was observed that the treatment of an adenocarcinoma cervical cancer cell line, HeLa with 20 μg/ml of the ethanolic extract of Withania somnifera for 6 days resulted in demethylation of promoter of RARβ2 gene. However, treatment with Ocimum sanctum and Azadirachta indica (20μg/ml) did not cause the reversal of hypermethylation after 6 days of treatment. This is the first report to show the reversal of hypermethylation of RARβ2 gene by Withania somnifera extract in a cervical cancer cell line.

Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells

Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

Study on methylation status of RASSFIA gene promoter and exon 1 in cervical cancer cell lines / 中国癌症杂志

Background and purpose:Loss or altered expression of Ras association domain family 1A gene (RASSF1A) through DNA methylation has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. This study aimed to explore the effect of DNA methyltransferase inhibitor 5-Aza-2’deoxycytidine (5-Aza-dc) on demethylation and expression of RASSF1A in cervical cancer cell lines. Methods:HPV positive cervical cancer cell lines HeLa and Caski, HPV negative cell lines HT-3 and C-33A were treated with two different concentration of 5-Aza-dc (5 μmol/L, 10 μmol/L). MSP (methylation-specific PCR) and Bisulfite genomic sequencing PCR (BGS) combined with TA clone were used to investigate methylation status of RASSF1A gene promoter and exon 1 before and after treatment of 5-Aza-dc. RASSF1A gene mRNA expression was detected by RT-PCR. Results:Two HPV positive cell lines showed hypomethylated RASSF1A promoters and expressed RASSF1A mRNA, and after treatment with 5-Aza-dc, the mRNA expression of RASSF1A did not change significantly (FHeLa=3.003, P=0.125; FCaski=0.045, P=0.956). Two HPV negative cervical cancer cell lines showed hypermethylation status of RASSF1A promoter and silenced RASSF1A. After treatment with 5-Aza-dc, demethylation occurred in the promoter region of RASSF1A gene, which subsequently induced re-expression of this gene in HT-3 and C-33A. The F test (FHT-3=18.002, P=0.03;FC-33A=17.179, P=0.03) and LSD-t test (P<0.05) demonstrated that significant difference in the expression of RASSF1A was found upon two different concentrations drug treatment.Conclusion:The methylation status of promoter and exon 1 of RASSFIA gene in HPV positive and HPV negative cervical cancer cell lines are different. The promoter hypermethylation is correlated with RASSF1A gene expression in HPV negative cervical cancer cell line HT-3 and C-33A, and plays a key role in RASSF1A silencing. 5-Aza-dc may effectively reverse the methylation status of RASSFIA gene promoter in cervical cancer HT-3 and C-33A cells and reactivate gene expression silenced by aberrant hypermethylation in a dose-dependent manner within certain extent.

Effect of folate in modulating the expression of DNA methyltransferase 1 and methyl-CpG-bingding protein 2 in cervical cancer cell lines / 中华流行病学杂志

Objective To explore the effects of folate on the expression of DNA methyltransferase 1 (DNMT1) and methyl-CpG-bingding protein 2 (MeCP2) in cervical cancer cell lines.Methods Experimental study was carried out in vitro.Human cervical cancer cell lines,including C33A cell with HPV negative and Caski cell with HPV16 positive,were treated with different concentration of folate.The expression of DNMT1 and MeCP2 protein (by Western blot)and mRNA (by real-time PCR) were then detected in the two cell lines.Results It was found that supplement of folate was able to reduce the cell proliferation in C33A cell (r=0.984,P＜0.001) and Caski cell (r=0.978,P=0.002),as well as induced the cell apoptosis (C33A:r=0.989,P＜0.001 ;Caski:r=0.994,P＜0.001).Results showed that the expression levels of DNMT1 protein (C33A:r=-0.914,P＜ 0.001 ; Caski:r=-0.859,P=0.003) and MeCP2 protein (C33A:r=-0.830,P=0.005 ;Caski:r=-0.981,P＜0.001) decreased gradually with the increase of folate concentrations,but the expression of DNMT1 and MeCP2 mRNA was not observed in Caski or C33A cell.When at the same levels of folate,the expression of DNMT1 protein or mRNA was higher in Caski cell than in C33A cell.However,the expression of MeCP2 protein or mRNA was higher in C33A cell than in Caski cell.Conclusion Our fimding indicated that adequate foleta could effectively inhibit the proliferation of cervical cancer cells and facilitate their apoptosis in vitro,thus would reverse the aberration protein expression of DNMTl and MeCP2.That there might be a synergistic action between HPV16 infection and parafunction of DNMT l in cervical cancer,being noticed.

The anti proliferative effect of palm oil ?-tocotrienol involves alterations in MEK-2 and ERK-2 protein expressions in CaSki cells.

Background: Vitamin E is a potent growth inhibitor of various cancer cell types in vitro and in vivo. The cell death mechanism is believed to be via cell cycle blockage, differentiation, and apoptosis. Objectives: To determine the possible involvement of protein expression of MEK-2 and ERK-2 in the cell death mechanism induced by palm oil ?-tocotrienol and ?-tocopherol in human cervical cancer cell line, CaSki cells. Methods: In this study, we tested the effect of ?-tocotrienol and ?-tocopherol on the proliferation and apoptosis in CaSki cells. Western blot analysis was used to determine the involvement of MEK-2 and ERK-2 in regulating the cell death mechanism. Results: Gamma-tocotrienol and α-tocopherol efficiently inhibited the proliferation of CaSki cells by 85.2% to 90.8% (p<0.01, n=4) and 10.2% to 39.1% (p<0.01, n=4) beginning at 100 μM and 50 μM, respectively. The possible cell death mechanism induced by both compounds may be due to apoptosis as confirmed by the presence of cellular DNA fragments separated by electrophoresis and enhancement of apoptotic activity. Treatment with γ-tocotrienol at 150 μM markedly decreased the protein expression of MEK-2 and ERK-2 at 12 hours and 18 hours. In contrast, treatment with α-tocopherol at 300μM has no effect on both protein expressions. Conclusion: The transient decreases in the protein expression of MEK-2 and ERK-2 suggested that the anti proliferative effect of γ-tocotrienol might involve alteration of the proliferative signaling cascade.

Detection of p16(INK4A) in the Mixed Cell Populations of Normal Peripheral Blood Mononuclear Cells and Cervical Cancer Cell Lines / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Human papilloma viruses (HPVs) play a central role in the pathogenesis of neoplastic lesions of the uterine cervix. The viral oncoprotein HPV E6 degrades the p53 protein, and the HPV E7 protein inactivates pRB and increases the expression of the CDK inhibitor, p16(INK4A). We investigated the usefulness of p16(INK4A) as a biologic marker for the cervical dysplastic and neoplastic cells. MATERIALS AND METHODS: We examined the expression of p16(INK4A) and cytokeratin in a mixed population of normal peripheral blood mononuclear cells (PBMC) and the cervical cancer cell lines (HeLa, SiHa, and CasKi) using flow cytometry. RESULTS: The DNA indices of the HeLa, SiHa and CasKi cell lines were 1.89, 1.53 and 1.75, respectively, indicating that these cells are aneuploid cells. Furthermore, the positive rate of p16(INK4A) expression was 86.7% for the HeLa mixed population, 85.6% for the SiHa mixed population, and 92.2% for the CasKi mixed population. According to the FL3A vs FL3W histogram, electrical gating of the HeLa, SiHa and CasKi mixed populations showed the expression levels of both cytokeratin and p16(INK4A) to be identical, at 86.6%, 84.8% and 85.0%, respectively. These findings revealed that almost all cells selected through electrical gating were cervical cancer cells originating from the epithelium and which expressed cytokeratin and p16(INK4A). On the other hand, when each mixed population was electrically gated for normal PBMC, we found that the PBMCs expressed neither cytokeratin nor p16(INK4A). CONCLUSION: Using flow cytometry, we observed the enhanced expression of p16(INK4A) in cervical cancer cell lines. These RESULTS suggest the usefulness of p16(INK4A) for the selective detection of cervical dysplastic and cancer cells in the liquid-based samples, which are taken from the cervices and contaminated with blood and stromal cells.

cDNA Microarray Expression Analysis in HPV-Infected Uterine Cervical Cancer Cell Line / 대한산부인과학회잡지

OBJECTIVE: To estimate the difference in gene expression related to carcinogenesis between HPV 16 positive squamous cell carcinoma and HPV 16 positive adenocarcinoma of cervix. METHODS: We used cDNA microarray technology to identify alterations in gene expression of human cervical cancers. Gene expression of three cell lines, CaSki and SiHa (HPV 16 positive squamous cell carcinoma) and HeLa (HPV 16 positive adenocarcinoma) were compared with HT3 (HPV 16 negative squamous cell carcinoma). The microarray contains twin spots for 344 cancer-associated genes. RESULTS: The analysis showed several interesting findings: (1) In all three squamous cell lines, CD4, CSF1, MMP15 and TNFR6 were increased, whereas SLC3A2 were decreased, (2) Only in adenocarcinoma cell line HeLa, CDC25A, CDK2, CDK9, IL2, PF4, MAD, FCER2, MAP4K1 and MS4A1 were increased, and PLAU, IL8, IL9R and ATK were decreased. (3) In both squamous cell carcinoma cell lines CaSki and SiHa, 61 genes which belong to chemokine, cell cycle, growth factor, interleukin, adhesion molecule, protein kinase and TNF were increased, whereas 10 genes which are associated with apoptosis and cytokine were increased only in SiHa, and 97 genes which are associated with a variety of cell functions were increased only in CaSki. CONCLUSION: We suggest that there might be common, but also different carcinogenic mechanisms involved in HPV 16 related cervical cancers according to the histologic subtypes and different tumors.

The Gene Expression Profile Using cDNA microarray after treatment Arsenic Compound (As2O3, As4O6) in SiHa Cell / 대한산부인과학회잡지

OBJECTIVE: To obtain information on the growth inhibition effect of arsenic compounds and gene expression profiles using cDNA microarray technique in SiHa cell lines. METHODS: We cultured 103 SiHa cell in 96 well plate and we investigated growth inhibition effects using MTT assay and also we performed gene expression profile experiment using 384 cDNA chip in SiHa cell after exposure of arsenics (As2O3, As4O6 - 1 (micro)M) for 48 hrs. RESULTS: Arsenics (As2O3, As4O6) inhibit the growth of SiHa cells (As2O3: 0.5, 1, 2, 3, 4, 5 (micro)M - 9.2, 56, 89, 93, 96, 96%, As4O6: 0.5, 1, 2, 3, 4, 5 (micro)M- 54, 84, 84, 85, 85, 87%) in 4 days culture. As2O3 and As4O6 induced apoptosis in SiHa cells. After exposure of As2O3, 47 genes were changed more than 2 times (eg, thymidylate synthetase, cyclin B1, CDC 20). In case of As4O6, 78 genes were changed more than 2 times (eg, CDC 20, cyclin B1, primase, proliferating cell nuclear antigen). CONCLUSION: we observed arsenic compound (As2O3, As4O6) inhibit the growth of SiHa cell. In gene expression profiling experiment, 78 genes was changed the expression level 2 times more than that of reference RNA after treatment of As4O6 and 47 genes after treatment of As2O3. Through these result, we thought more study need in functional genomics after arsenic treated cervical cancer cells.

Combined Effect of Radiation and Tyrphostin AG 1478 in Human Cervical Cancer Cell Lines / 대한산부인과학회잡지

OBJECTIVE: We studied the possibility that addition of Tyrphostin AG 1478 which is selective epidermal growth factor inhibitor, would enhance the effect of radiation on human cervical cancer cell lines, HeLa and CaSki. METHODS: Tyrphostin was added to the cells which were irradiated. The ratio of dead cells was estimated by trypan blue dye examination, and survived cell fractions were estimated by clonogenic assays. The presence and degree of apoptosis were examined by DNA electrophoresis and nuclear dye using propium iodide. RESULTS: The growth was completely inhibited in both cell lines, but the addition of tyrphostin resulted in different effects on the radiation induced cell death and apoptosis in each cell line. However, the percentage of dead cells and apoptotic cells was decreased in HeLa cell line compared with CaSki cell line. The ultimate survived cell fractions determined by clonogenic assays were decreased in both cell lines and the size of colony was also decreased. CONCLUSION: These data suggest that the addition of Tyrphostin is able to increase the radiotherapeutic effects on human cervical cancer cells, and this synergistic effect may result from effective blocking of radiation-induced accelerated repopulation of cancer cells by tyrphostin.

The Mechanisms of the Antiproliferative Effect by Interferon- a in Cervical Cancer Cell Lines / 대한부인종양콜포스코피학회잡지

Interferons(IFNs) exhibit an antiproliferative effect on many normal and transformed cells and have in vivo antitumor activity in a variety of cancers. Recent clinical studies have suggested major activity with IFNs, especially in advanced squamous cell carcinoma of the skin and cervix. With the objective of exploring how the IFNs might work in squamous carcinoma cell line, we studied the effect of IFN-a on cervical cancer cell lines. The effect of IFNs on apoptosis and cell cycle of cervical cancer cell lines(C33A, CaSki, SiHa, HeLa, ME-180) was analysed by flow cytometry in time dependent manner. Results were as follows: (1) According to cell count of studied cancer cell lines treated with 2,000 IU/ml IFN-a for 7 days exposure, IFN-a had the antiproliferative effect on all five tested cervical cancer cell lines. Also this antiproliferative effect was confirmed by WST-1 assay. (2) The effect of IFN-a on apoptosis of each cultute was analysed by flow cytometry after 3 days and 7 days exposure with 2,000 IU/ml IFN-a, Apoptosis was not induced by IFN-a treatment. (3) The effect of IFN-a on the cell cycle of each culture was analysed by flow cytometry after 3 days exposure with 2,000 IU/ml IFN-a. As compared to control cells, treatment with IFN-a resulted in a higher proportion of cells in S phase with lower portion of cells with G2/M phase. (4) Time course of IFN-a effect on HPV 16 and HPV 18 E6 mRNA levels was evaluated by northern blot analysis. In CaSki cell line, HPV 16 E6 mRNA expression induced by IFN-a was not inhibited. But in HeLa cell line, HPV 18 E6 inRNA expression was inhibited. IFN-a appears to have the antiproliferative effect on all five tested cervical cancer cell lines and the antiproliferative effect of IFN-a seemed to be induced not by apoptosis but by disruption on specific cell cycle. Also regulation of HPV E6 mRNA expression induced by IFN-a is not directly related to the mechanisms of the antiproliferative effect of IFN-a in cancer cell lines.