文献类型：期刊文献

英文题名：ML216-Induced BLM Helicase Inhibition Sensitizes PCa Cells to the DNA-Crosslinking Agent Cisplatin

作者：Ma, Xiao-Yan Zhao, Jia-Fu Ruan, Yong Zhang, Wang-Ming Zhang, Lun-Qing Cai, Zheng-Dong Xu, Hou-Qiang

第一作者：Ma, Xiao-Yan;马小彦

通信作者：Xu, HQ[1];Xu, HQ[2]

机构：[1]Guizhou Univ, Coll Life Sci, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Minist Educ, Guiyang 550025, Peoples R China;[2]Guizhou Inst Technol, Coll Food & Pharmaceut Engn, Guiyang 550003, Peoples R China;[3]Guizhou Univ, Coll Anim Sci, Guiyang 550025, Peoples R China;[4]Guizhou Med Univ, Basic Med Coll, Dept Immunol, Guiyang 550014, Peoples R China

第一机构：Guizhou Univ, Coll Life Sci, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Minist Educ, Guiyang 550025, Peoples R China

通信机构：corresponding author), Guizhou Univ, Coll Life Sci, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Minist Educ, Guiyang 550025, Peoples R China;corresponding author), Guizhou Univ, Coll Anim Sci, Guiyang 550025, Peoples R China.

年份：2022

卷号：27

期号：24

外文期刊名：MOLECULES

收录：;Scopus(收录号：2-s2.0-85144548003);WOS:【SCI-EXPANDED(收录号:WOS:000902863300001)】；

基金：This research was funded by the National Natural Science Foundation of China, chaired by Hou-Qiang Xu, with grant number 31860242. This research was also funded by Guizhou Province Science and Technology Plan Project, chaired by Xiao-Yan Ma, with grant number [2019]1136.

语种：英文

外文关键词：BLM inhibitor; ML216; CDDP; combined therapy

摘要：Using standard DNA-damaging medicines with DNA repair inhibitors is a promising anticancer tool to achieve better therapeutic responses and reduce therapy-related side effects. Cell viability assay, neutral comet assay, western blotting (WB), and cell cycle and apoptosis analysis were used to determine the synergistic effect and mechanism of ML216, a Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, in PCa cells. Based on the online database research, our findings revealed that BLM was substantially expressed in PCa, which is associated with a bad prognosis for PCa patients. The combination of ML216 and CDDP improved the antiproliferative properties of three PCa cell lines. As indicated by the increased production of gamma H2AX and caspase-3 cleavage, ML216 significantly reduced the DNA damage-induced high expression of BLM, making PC3 more susceptible to apoptosis and DNA damage caused by CDDP. Furthermore, the combination of ML216 and CDDP increased p-Chk1 and p-Chk2 expression. The DNA damage may have triggered the ATR-Chk1 and ATM-Chk2 pathways simultaneously. Our results demonstrated that ML216 and CDDP combination therapy exhibited synergistic effects, and combination chemotherapy could be a novel anticancer tactic.