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携带 SPAG9-shRNA 的溶瘤腺病毒增强了多西他赛治疗晚期前列腺癌的疗效。

Oncolytic adenovirus carrying SPAG9-shRNA enhanced the efficacy of docetaxel for advanced prostate cancer.

机构信息

Department of Urinary Surgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

出版信息

Anticancer Drugs. 2022 Feb 1;33(2):142-148. doi: 10.1097/CAD.0000000000001251.

DOI:10.1097/CAD.0000000000001251
PMID:34561997
Abstract

Sperm-associated antigen 9 (SPAG9) is closely related to the growth and metastasis of advanced prostate cancer. Docetaxel (DTX) is the gold standard for chemotherapy of prostate cancer, but its side effects decrease the life quality of patients. Therefore, it is urgent to develop combination therapy to increase chemotherapy efficacy for advanced prostate cancer. Oncolytic adenovirus carrying a short hairpin RNA (shRNA) targeting SPAG9 (ZD55-shSPAG9) was applied alone or in combination with docetaxel in prostate cancer cells. Cells were analyzed by cell counting kit-8, Hocehst-33258, transwell and western blot analysis. For in vivo experiments, nude mice were loaded with prostate cancer cells. ZD55-shSPAG9 effectively silenced the expression of SPAG9 in prostate cancer cells in vitro and in vivo. The replication of ZD55-shSPAG9 in prostate cancer cells was not affected by docetaxel, but the combined use of ZD55-shSAPAG9 and docetaxel has a better inhibitory effect on tumor growth and invasion in vitro and in vivo. Our study showed that the combined use of ZD55-shSPAG9 and docetaxel may be a new approach to the treatment of advanced prostate cancer.

摘要

精子相关抗原 9(SPAG9)与晚期前列腺癌的生长和转移密切相关。多西他赛(DTX)是前列腺癌化疗的金标准,但它的副作用降低了患者的生活质量。因此,迫切需要开发联合治疗方法来提高晚期前列腺癌的化疗疗效。携带靶向 SPAG9 的短发夹 RNA(shRNA)的溶瘤腺病毒(ZD55-shSPAG9)单独或联合多西他赛应用于前列腺癌细胞中。通过细胞计数试剂盒-8、Hocehst-33258、Transwell 和 Western blot 分析来分析细胞。对于体内实验,裸鼠负载前列腺癌细胞。ZD55-shSPAG9 有效沉默了前列腺癌细胞中 SPAG9 的表达,无论是在体外还是体内。ZD55-shSPAG9 在前列腺癌细胞中的复制不受多西他赛的影响,但 ZD55-shSAPAG9 和多西他赛的联合使用对体外和体内肿瘤生长和侵袭具有更好的抑制作用。我们的研究表明,ZD55-shSPAG9 和多西他赛的联合使用可能是治疗晚期前列腺癌的一种新方法。

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