Bi Huan, Zhang Zetian, Guo Li, Fu Cheng
Department of Urology Surgery, Liaoning Cancer Hospital and Institute, Shenyang 110042, China.
Department of Technology, Shenyang Yike Biotechnology Co., Ltd, Shenyang 110000, China.
Oncotarget. 2017 Jun 28;8(38):63258-63264. doi: 10.18632/oncotarget.18791. eCollection 2017 Sep 8.
The present study investigated the effect of zeste homolog 2 (EZH2) and wound fluid (WF) on chemotherapy sensitivities of T24 bladder cancer cells by using a collagen gel droplet embedded culture-drug sensitivity test (CD-DST). T24 bladder cancer cells with different EZH2 expression levels were co-cultured with postoperative WF from patients with bladder cancer. The CD-DST was performed to detect the sensitivity of tumor cells to gemcitabine and cis-diamminedichloridoplatinum (II) (cisplatin, DDP). The survival rates of the bladder cancer cells were used to determine the drug's chemotherapeutic effect. EZH2 knockdown increased the sensitivity of the cells to gemcitabine and DDP, whereas EZH2 overexpression decreased the chemotherapeutic sensitivity. Except for the situation of EZH2 overexpression, co-culturing with WF induced significantly higher drug resistance in tumor cells. Overexpression of EZH2 and surgery-induced WF promoted the drug resistance of bladder cancer cells to the investigated chemotherapeutic agents, suggesting that more studies are needed to investigate the key mechanisms underlying the EZH2- and WF-induced reduction of susceptibility to chemotherapy drugs.
本研究采用胶原凝胶微滴包埋培养-药物敏感性试验(CD-DST),探讨zeste同源物2(EZH2)和伤口渗出液(WF)对T24膀胱癌细胞化疗敏感性的影响。将不同EZH2表达水平的T24膀胱癌细胞与膀胱癌患者术后的WF共同培养。进行CD-DST以检测肿瘤细胞对吉西他滨和顺二氯二氨合铂(II)(顺铂,DDP)的敏感性。通过膀胱癌细胞的存活率来确定药物的化疗效果。EZH2基因敲低增加了细胞对吉西他滨和DDP的敏感性,而EZH2过表达则降低了化疗敏感性。除EZH2过表达的情况外,与WF共同培养可显著诱导肿瘤细胞产生更高的耐药性。EZH2过表达和手术诱导产生的WF促进了膀胱癌细胞对所研究化疗药物的耐药性,这表明需要更多研究来探究EZH2和WF导致化疗药物敏感性降低的关键机制。