Chemotherapeutics-induced Oct4 expression contributes to drug resistance and tumor recurrence in bladder cancer

Chia Sing Lu, Gia Shing Shieh, Chung Teng Wang, Bing Hua Su, Yu Chu Su, Yi Cheng Chen, Wu Chou Su, Pensee Wu, Wen Horng Yang, Ai Li Shiau, Chao Liang Wu

研究成果: 雜誌貢獻文章

15 引文 斯高帕斯(Scopus)

摘要

Cancer cells initially characterized as sensitive to chemotherapy may acquire resistance to chemotherapy and lead to tumor recurrence through the expansion of drug-resistant population. Acquisition of drug resistance to conventional chemotherapy is a major obstacle in the treatment of recurrent cancer. Here we investigated whether anticancer drugs induced Oct4 expression, thereby contributing to acquired drug resistance and tumor recurrence in bladder cancer. We identified a positive correlation of Oct4 expression with tumor recurrence in 122 clinical specimens of superficial high-grade (stages T1-2) bladder transitional cell carcinoma (TCC). Increased Oct4 levels in bladder tumors were associated with short recurrence-free intervals in the patients. Chemotherapy induced Oct4 expression in bladder cancer cells. Notably, treatment with cisplatin increased CD44-positive bladder cancer cells expressing Oct4, representing cancer stem-like cell subpopulation. Forced expression of Oct4 reduced, whereas knockdown of Oct4 enhanced, drug sensitivity in bladder cancer cells. Furthermore, tumor cells overexpressing Oct4 responded poorly to cisplatin in vivo. In regard to clinical relevance, inhibition of Oct4 by all-trans retinoic acid (ATRA) synergistically increased sensitivity to cisplatin in bladder cancer cells. Furthermore, the combination of cisplatin and ATRA was superior to cisplatin alone in suppressing tumor growth. Therefore, our results provide evidence that Oct4 increases drug resistance and implicate that inhibition of Oct4 may be a therapeutic strategy to circumvent drug resistance.
原文英語
頁(從 - 到)30844-30858
頁數15
期刊Oncotarget
8
發行號19
DOIs
出版狀態已發佈 - 一月 1 2017
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Oncology

引用此

Lu, C. S., Shieh, G. S., Wang, C. T., Su, B. H., Su, Y. C., Chen, Y. C., Su, W. C., Wu, P., Yang, W. H., Shiau, A. L., & Wu, C. L. (2017). Chemotherapeutics-induced Oct4 expression contributes to drug resistance and tumor recurrence in bladder cancer. Oncotarget, 8(19), 30844-30858. https://doi.org/10.18632/oncotarget.9602