Chinese Clinical Oncology

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Effects of different cisplatin chemotherapy patterns on vasculogenic mimicry of ovarian cancer cell SKOV3 and the possible mechanisms

WU Xiaohua,CHEN Lin,SUN Yanan   

  1. Department of Gynecology and Obstetrics, Bethune International Peace Hospital of People’s Liberation Army, Shijiazhuang 050082, China
  • Received:2016-04-04 Revised:2016-06-05 Online:2016-08-31 Published:2016-08-31

Abstract: Objective To explore the effects of low-dose metronomic chemotherapy(LDM)and maximum tolerated-dose chemotherapy(MTD)on vasculogenic mimicry(VM)of ovarian epithelial cancer cell SKOV3 and the possible mechanisms. Methods The primary tumor cells were obtained through injecting cisplatin by different chemotherapy schedules(LDM,MTD and control group without chemotherapy)in the nude mice bearing SKOV3 ovarian cancer xenografts. Three groups of primary cells were cultured in threedimensional cell culture model to compare the VM formation ability. The proliferative and invasive ability of each group was evaluated by MTT and Transwell chamber test in vitro respectively. The expression level of CD133 and aldehyde dehydrogenase1(ALDH1)in the primary cells were analyzed by Western blotting and VM formation differences of CD133+ALDH1+cells and CD133-ALDH1-cells were observed by fluorescence-activated cell sorting(FACS). Results The tumor inhibition rates of MTD group and LDM group were 25.87% and 51.52%. Primary tumor cells formed VM in MTD group in only about 6 hours, while in control group and LDM group were 9 hours and 12 hours respectively. After 48 h,the vasculogenic mimicry density(VMD)of MTD group,control group and LDM group was 29.60±9.55,18.70±4.97 and 11.20±2.60,with statistical significance(P<0.05). Compared to LDM group and control group,the cell proliferation of MTD group was significantly higher from the third day(P<0.05). Transwell chamber test showed that the cells of LDM group got through the maxtrix film was 87.33±19.58,much less than 156.93±22.77 of MTD group and 112.13±16.59 of control group(P<0.05). Western blotting suggested that the levels of CD133 and ALDH1 proteins in primary tumor cells of MTD group were 0.402±0.034 and 0.418±0.020,in control group were 0.338±0.046 and 0.325±0.011,in LDM group were 0.296±0.042 and 0.318±0.012. The differences among the 3 groups had statistic significance(P<0.05). When CD133+ALDH1+cells and CD133-ALDH1-cells were cultured with the same density of 5×104/ml,the former formed VM within 6 h,while the latter did not form any after 48 h. Little VM was observed after 24 h when CD133-ALDH1-cells were cultured with the density of 1×105/ml. Conclusion The tumor cells with partial tumor stem cell properties to be enriched easier in MTD than in LDM probably. These cells could influence the tumor blood supply and result in bad prognosis.

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