title: Knockdown of SALL4 inhibits the proliferation and reverses the resistance of MCF-7/ADR cells to doxorubicin hydrochloride.
abstract: BACKGROUND
  Breast cancer is the most frequent malignancy in women and drug resistance is the major obstacle for its successful chemotherapy. In the present study, we analyzed the involvement of an oncofetal gene, sal-like 4 (SALL4), in the tumor proliferation and drug resistance of human breast cancer.
  
  
  RESULTS
  Our study showed that SALL4 was up-regulated in the drug resistant breast cancer cell line, MCF-7/ADR, compared to the other five cell lines. We established the lentiviral system expressing short hairpin RNA to knockdown SALL4 in MCF-7/ADR cells. Down-regulation of SALL4 inhibited the proliferation of MCF-7/ADR cells and induced the G1 phase arrest in cell cycle, accompanied by an obvious reduction of the expression of cyclinD1 and CDK4. Besides, down-regulating SALL4 can re-sensitize MCF-7/ADR to doxorubicin hydrochloride (ADMh) and had potent synergy with ADMh in MCF-7/ADR cells. Depletion of SALL4 led to a decrease in IC50 for ADMh and an inhibitory effect on the ability to form colonies in MCF-7/ADR cells. With SALL4 knockdown, ADMh accumulation rate of MCF-7/ADR cells was increased, while the expression of BCRP and c-myc was significantly decreased. Furthermore, silencing SALL4 also suppressed the growth of the xenograft tumors and reversed their resistance to ADMh in vivo.
  
  
  CONCLUSIONS
  SALL4 knockdown inhibits the growth of the drug resistant breast cancer due to cell cycle arrest and reverses tumor chemo-resistance through down-regulating the membrane transporter, BCPR. Thus, SALL4 has potential as a novel target for the treatment of breast cancer.
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. yuanyuanchen124@126.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. yuanyuanchen124@126.com.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. lizhizhenlee@163.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. lizhizhenlee@163.com.
authors.forename: Zhi-Zhen
authors.initials: ZZ
authors.lastname: Li
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. yeyuanyuan19891028@126.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. yeyuanyuan19891028@126.com.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ye
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. 71286633@qq.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. 71286633@qq.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. twinkleniu@163.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. twinkleniu@163.com.
authors.forename: Rui-Jie
authors.initials: RJ
authors.lastname: Niu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. 645034727@qq.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. 645034727@qq.com.
authors.forename: Hong-Chen
authors.initials: HC
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. sunshinezyj@126.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. sunshinezyj@126.com.
authors.forename: Yi-Jian
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. 1019061239@qq.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. 1019061239@qq.com.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kong Jiang Road, 200092, Shanghai, China. phdhanbaosan@126.com.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, 200092, Shanghai, China. phdhanbaosan@126.com.
authors.forename: Bao-San
authors.initials: BS
authors.lastname: Han
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D051379:Mice; D014157:Transcription Factors / Q000235:genetics*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C472575:SALL4 protein, human; D014157:Transcription Factors; D004317:Doxorubicin