title: Silencing of the ABCC4 gene by RNA interference reverses multidrug resistance in human gastric cancer.
abstract: The identification of genes associated with recurrent drug resistance in gastric cancer and the elucidation of the underlying molecular mechanisms associated with recurrent drug resistance in gastric cancer are important for the effective treatment and prognosis of this cancer. Variations in the expression level of the ATP-binding cassette subfamily C member 4 (ABCC4) gene are correlated with the recurrence, development and chemotherapeutic susceptibility of various types of cancers. In the present study, we demonstrated that the ABCC4 gene was highly expressed in multiple types of gastric cancer cells, and ABCC4 expression was even more prominent in the drug-resistant gastric cancer cells. Conversely, in normal gastric mucosal cells, ABCC4 expression was very low or undetectable. We used RNA interference to decrease the expression of ABCC4 in drug-resistant gastric cancer cells, which resulted in an increase in apoptosis and cell cycle arrest in the G1 phase. In addition, we found that ABCC4 knockdown in 5-fluorouracil (5-FU)-resistant cancer cells restored 5-FU sensitivity, resulting in the inhibition of cell proliferation and tumour growth in nude mice. Our results showed that inhibition of ABCC4 gene expression can inhibit the proliferation of multidrug-resistant gastric cancer cells and can enhance gastric cancer cell sensitivity to chemotherapeutic drugs.
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, P.R. China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, P.R. China.
authors.forename: Zhenran
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Southwest Hospital of the Third Military Medical University, Shapingba, Chongqing 400038, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, P.R. China.
authors.forename: Chaowen
authors.initials: C
authors.lastname: Sun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics*; D014162:Transfection
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C073492:ABCC4 protein, human