Sun Shujun, Jiang Kehua, Zeng Jin
Queen Mary School, Nanchang University, Nanchang, China.
Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
Transl Androl Urol. 2022 Sep;11(9):1336-1344. doi: 10.21037/tau-22-543.
To investigate the potential mechanisms of chemoradiotherapy resistance in patients with bladder cancer.
We assessed three bladder cancer cell lines (5637, J82, and TCCSUP) for their sensitivity to chemoradiotherapy. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the expression of specific genes after chemoradiotherapy or combined with olaparib. The Genome Cancer Atlas (TGCA) database was used to analyze possible radioresistance-related genes and the relationship between their expression and bladder cancer survival and prognostic indicators.
The 5637 cell line showed the most significant sensitivity to chemoradiotherapy. The expression levels of DNA damage repair genes in 5637 cells did not significantly change after chemoradiotherapy. In contrast, the expression levels of and genes significantly increased in J82 and TCCSUP cells after chemoradiotherapy. After combination with olaparib, which is a poly (ADP-ribose) polymerase inhibitor that initiates DNA repair, 5637 cells were significantly inhibited by chemoradiotherapy. However, chemoradiotherapy inhibition on J82 cells was weakened when combined with olaparib. A high reactive expression of and after combination with olaparib suggested that olaparib was ineffective because it did not induce synthetic lethality in which inhibiting PARP by olaparib coincided with suppression of BRCA1/2 expression result in cancer cell death.
The expression levels of and genes were associated with sensitivity to radiotherapy and chemotherapy in bladder cancer, and an increase in reactive expression after treatment led to worse sensitivity. Therefore, the reactive expression levels of and after chemoradiotherapy may be useful in evaluating the efficacy of olaparib combination therapy.
探讨膀胱癌患者放化疗耐药的潜在机制。
我们评估了三种膀胱癌细胞系（5637、J82和TCCSUP）对放化疗的敏感性。采用逆转录定量聚合酶链反应（RT-qPCR）检测放化疗后或联合奥拉帕利后特定基因的表达。利用基因组癌症图谱（TGCA）数据库分析可能的放疗抵抗相关基因及其表达与膀胱癌生存和预后指标之间的关系。
5637细胞系对放化疗表现出最显著的敏感性。5637细胞中DNA损伤修复基因的表达水平在放化疗后无显著变化。相比之下，J82和TCCSUP细胞在放化疗后 和 基因的表达水平显著升高。与启动DNA修复的聚（ADP-核糖）聚合酶抑制剂奥拉帕利联合使用后，5637细胞受到放化疗的显著抑制。然而，与奥拉帕利联合使用时，放化疗对J82细胞的抑制作用减弱。与奥拉帕利联合使用后 和 的高反应性表达表明奥拉帕利无效，因为它没有诱导合成致死，即奥拉帕利抑制PARP与抑制BRCA1/2表达同时发生导致癌细胞死亡。
和 基因的表达水平与膀胱癌对放疗和化疗的敏感性相关，治疗后反应性表达增加导致敏感性降低。因此，放化疗后 和 的反应性表达水平可能有助于评估奥拉帕利联合治疗的疗效。
