Hyperthermia On Cisplatin Sensitivity Of Ovarian Cancer And Its Mechanism In Vitro

ObjectiveTo investigate the proliferation inhibitory effect of hyperthermia combined with cisplatin on human ovarian carcinoma SKOV3cells and SKOV3/DDP cells at different temperature(ordinary temperature、41℃),different time(41℃30min、60min、90min、120min). Then we will study whether hyperthermia combined with cisplatin could enhance the sensitivity and reverse the drug-resistance. And we detected the expression of ERCC1in SKOV3and SKOV3/DDP cells when hyperthermia combined with cisplatin at different temperature and different times to analyze its mechanism.To provide experimental basis to intraperitoneal hypertnermic chemotherapy combined with cisplatin could increase sensitivity and reverse the cisplatin-resistant on ovarian cancer. Meanwhile this could provide new methods to reduce recurrence and improve prognosis of patients with ovarian cancer in clinical.Methods。1MTT was used to study the cell proliferation and the inhibition rates on SKOV3and SKOV3/DDP cells.2We estimated the expression of ERCC1gene in SKOV3and SKOV3/DDP cells by western bloting to analyze the mechanism of hyperthermia combined with cisplatin.Results1The proliferation inhibition effect of hyperthermia on ovarian cancer cells.①Hyperthermia has proliferation inhibition effect on SKOV3cells. While24h, under41℃for different times the effects of inhibition on SKOV3cells have statistically significant difference (F=17.806, P=0.001), and there was statistically difference between under41℃90min and120min, significantly (P<0.001).At the time of48h and72h, under41℃for different times, the effects of inhibition on SKOV3cells have statistically significant difference (F=28.951; F=29.196, P<0.001), the effects were increase under41℃60min and90min, significantly (P<0.001). The proliferation inhibition effect can last to72hours. ②Hyperthermia has proliferation inhibition effect on SKOV3/DDP cells. While24h, under41℃for different times, the effects of inhibition has no statistically difference (F=3.547,P=0.068). At the time of48h, under41℃for different times, the effects of inhibition on SKOV3/DDP cells have statistically significant difference (F=18.135,P<0.001), the effects were increase under41℃60min and90min, significantly (P<0.001), but there was no difference between them.When comes to72h, under41℃for different times, the effects of inhibition on SKOV3/DDP cells have statistically difference (F=5.455,P<0.05). When the effects were compared under41℃30min with90min,60min with120min,90min with120min, the difference has statistical significance.2The contribution of hyperthermia on cisplatin sensitivity on ovarian cancer cells.①Hyperthermia combined with cisplatin at ordinary temperature and41℃different time,the sensitivity to cisplatin on SKOV3cells were different, significantly,(F=67.489,P<0.001). At41℃90min or less, the sensitivity to cisplatin on SKOV3cells increased with the time prolonging.And the increasing at41℃60min and90min has statistical significance (P<0.05), and41℃90min was higher than60min (P=0.002). At41℃120min and room temperature,41℃30min,60min,90min there was no statistically significant difference compared. The sensitivity of cisplatin on SKOV3cells was increased79.885%.②Hyperthermia combined with cisplatin at ordinary temperature and41℃different time,the sensitivity to cisplatin on SKOV3/DDP cells were different, significantly,(F=18.356,P<0.001).The sensitivity to cisplatin was higher at41℃than ordinary temperature. Within90min at41℃, the sensitivity to cisplatin on SKOV3/DDP cells increased with the time prolonging. The sensitivity to cisplatin at41℃120min was lower than90min.But there was no difference between41℃120min and30min、60min.41℃90min may be the optimal choice. The sensitivity of cisplatin on SKOV3/DDP cells was increased37.129%.3The expression of ERCC1gene SKOV3was lower than SKOV3/DDP significantly (F=32.175,P<0.001),but there was no difference between the ordinary temperature and41℃(30min、60mn、90min、120min) in both SKOV3and SKOV3/DDP cells (F=0.962,P=0.443). Conclusions1Thermotherapy has inhibitory effect to SKOV3and SKOV3/DDP cells;2Thermotherapy could increase the sensitivity on DDP of SKOV3and could reverse the drug-resistance on DDP of SKOV3/DDP.41℃,90min may be the optimal choice;3The expression of ERCC1in SKOV3was lower than SKOV3/DDP.But there was no difference between the ordinary temperature and the four time of41℃in both SKOV3and SKOV3/DDP cells, respectively. Hyperthermia may increase the sensitivity on DDP of SKOV3and reverse the drug-resistance on DDP of SKOV3/DDP through other way.