Effects Of Verteporfin On Human Cervical Carcinoma Cell And Preliminary Mechanism Study

Objective:The incidence of cervical cancer is increasing year by year and showing a trend of rejuvenation.Although platinum-based chemotherapy can alleviate the condition of cervical cancer,it compromised exquisitely the fertility of young patients.Accumulated evidences have shown that the photosensitizer with less reproductive toxicity may be an ideal medicine for cervical cancer patients with fertility desires.The aim of this study was to investigate the effect of the photosensitizer Verteporfin(VP)on human cervical carcinoma cells and to elucidate its possible mechanism of action.Methods: Human cervical carcinoma cells(He La and Si Ha cells)were treated with VP of different concentrations to investigate the effect of VP in vitro.Cell viability and migration ability were evaluated by CCK-8 and wound healing assay.Meanwhile,apoptosis rates were assessed by flow cytometry,Western blot and TUNEL staining.Tumor-bearing-mouse models were established to explore the effect of VP on human cervical cancer in vivo.Moreover,several critical molecules in endoplasmic reticulum stress(ER Stress)pathways were detected in VP-treated cells.In addition,ER Stress was inhibited to observe the effects on cell apoptosis.Results: The viability and migration ability of He La and Si Ha cells were suppressed by VP in dose-and time-dependent manners.Compared with control group,apoptosis rates were higher and the expression of the Caspase-3 was upregulated with Bcl-2/Bax decreased as well as stronger TUNEL fluorescence signal in the experimental group,which substantiated that VP could induce apoptosis in human cervical carcinoma cells at 2D and 3D levels.Besides,VP can squelch the growth of tumors in both sizes and weights in nude mice.Moreover,VP activated ER Stress by upregulating the expression of GRP78,CHOP and Caspase-12.Whereas,apoptosis was attenuated in VP-treated cells when ER Stress pathways were inhibited.Conclusion: VP inhibited the viability and migration of human cervical carcinoma cells effectively,and also induced apoptosis,which may achieve through ER stress pathways.VP may be a promising agent for cervical cancer patients with fertility desires,and more researches are required to support its application in clinic.