Basic & Clinical Medicine ›› 2022, Vol. 42 ›› Issue (7): 1060-1066.doi: 10.16352/j.issn.1001-6325.2022.07.1060

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Deleted in breast cancer 1(DBC1) affects the sensitivity of breast cancer cell lines to etoposide

HAN Xue-ying, CUI Feng, LI Jun*   

  1. Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China
  • Received:2022-03-23 Revised:2022-04-27 Online:2022-07-05 Published:2022-06-29
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Abstract: Objective To compare the sensitivity of deleted in breast cancer 1 (DBC1) in triple-negative breast cancer cell lines HCC-70 and MDA-MB-231 to DNA damage agents. Methods The HCC-70 cell strain with DBC1 knockdown was generated by lentivirus infection. Etoposide was used to induce DNA damage. The DNA damage repair proteins and cell cycle regulation proteins were detected by Western blot; the cell survival rates were detected by CCK8 test; the apoptosis was measured by flow cytometry. Results Etoposide changed cell survival rate and apoptosis of HCC-70 cells but not statistically significant, while the decrease of the survival rate and apoptosis level of MDA-MB-231 cells was significant (P< 0.001). There was a negative correlation between the expression of DBC1 protein in HCC-70 and MDA-MB-231 cells; after knocking down DBC1 in HCC-70 cells to close to the level of MDA-MB-231 cells, the level of Bloom's syndrom helicase(BLM), p21, cell survival rate (P<0.001) and apoptosis rate (P<0.01) were similar to those of MDA-MB-231 cells; the combination of ML216, an inhibitor of BLM, and etoposide significantly decreased the survival rate of MDA-MB-231 cells increased apoptosis (P<0.01). Conclusions DBC1 is able to affect the sensitivity of breast cancer cells to DNA damage reagent etoposide and ML216 can increase the sensitivity of etoposide to breast cancer cells with low expression of DBC1.

Key words: deleted in breast cancer 1 (DBC1), Bloom's syndrome helicase (BLM), apoptosis, ML216

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