Knockdown of UbcH10 enhances the chemosensitivity of dual drug resistant breast cancer cells to epirubicin and docetaxel.
Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10), may also play some roles in the genesis and development of breast cancer. In the current study, we found that the expression of UbcH10 was up-regulated in some breast cancer tissues and five cell lines. We established a dual drug resistant cell line MCF-7/EPB (epirubicin)/TXT (docetaxel) and a lentiviral system expressing UbcH10 shRNA to investigate the effects of UbcH10 knockdown on the chemosensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel. The knockdown of UbcH10 inhibited the proliferation of both MCF-7 and MCF-7/EPB/TXT cells, due to the G1 phase arrest in cell cycle. Furthermore, UbcH10 knockdown increased the sensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel and promoted the apoptosis induced by these two drugs. Protein detection showed that, in addition to inhibiting the expression of Ki67 and cyclin D1, UbcH10 RNAi also impaired the increased BCL-2 and MDR-1 expression levels in MCF-7/EPB/TXT cells, which may contribute to abating the drug resistance in the breast cancer cells. Our research in the current study demonstrated that up-regulation of UbcH10 was involved in breast cancer and its knockdown can inhibit the growth of cancer cells and increase the chemosensitivity of the dual drug resistant breast cancer cells to epirubicin and docetaxel, suggesting that UbcH10 may be a promising target for the therapy of breast cancer.
Department of Breast Surgery, Central Hospital of Huangpu District, Shanghai 20002, China. wangcheng1212@hotmail.com.
Cheng
C
Wang
Department of Breast Surgery, Central Hospital of Huangpu District, Shanghai 20002, China. panyunhao@gmail.com.
Yun-Hao
YH
Pan
Department of Breast Surgery, Central Hospital of Huangpu District, Shanghai 20002, China. shanming99@gmail.com.
Ming
M
Shan
Department of Pathology, Central Hospital of Huangpu District, Shanghai 20002, China. xujshan@sina.com.
Ming
M
Xu
Department of Breast Surgery, Central Hospital of Huangpu District, Shanghai 20002, China. huangpuruxian@163.com.
Jia-Lin
JL
Bao
Department of Respiratory Disease, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai 200433, China. 1976zlm@163.com.
Li-Ming
LM
Zhao
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D015251:Epirubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes