title: Association of ABCB1, β tubulin I, and III with multidrug resistance of MCF7/DOC subline from breast cancer cell line MCF7.
abstract: Docetaxel is a first-line chemotherapeutic agent for treating advanced breast cancer. The development of chemoresistance or multidrug resistance (MDR), however, results in breast cancer chemotherapy failure. This study aims to explore the molecular mechanisms underlying docetaxel-resistance in treatment of breast cancer. The docetaxel-resistant subline MCF7/DOC, derived from the parental sensitive breast cancer cell line MCF7, was established by intermittent exposure to moderate concentrations of docetaxel, followed by examination of its phenotypes. The MCF7/DOC subline showed cross resistance against paclitaxel, doxorubicin, methotrexate, and 5-Fu. Compared to the parental MCF7, MCF7/DOC cells were enlarged with heterogeneous sizes and a cobblestone and polygonal appearance. They were arrested at G2/M phase and proliferated slowly. The colony formation potential of MCF7/DOC in soft agar was significantly increased. MCF7/DOC cells showed reduced intracellular accumulation and increased efflux of rhodamine 123. The mRNA expression level of adenosine triphosphate binding cassette (ABC) transporter family, i.e., ABCB1, ABCC1, ABCC2, ABCG2, and β tubulin isotypes were characterized by quantitative PCR. High-level expression of ABCB1, βI, and βIII tubulin mRNA in MCF7/DOC was detected. Downregulation of ABCB1, βI, and βIII tubulin mediated by three combined siRNAs resulted in stronger growth inhibition of MCF7/DOC than inhibition of the expression of individual genes. ABCB1, βI, and βIII tubulin might contribute to the MDR of MCF7/DOC and be potential therapeutic targets for overcoming MDR of breast cancer.
authors.affiliation: Department of Breast Surgery, The People's Hospital of Henan Province (The People's Hospital of Zhengzhou University), Zhengzhou, China, 450000.
authors.forename: Wentao
authors.initials: W
authors.lastname: Li
authors.forename: Baoping
authors.initials: B
authors.lastname: Zhai
authors.forename: Hui
authors.initials: H
authors.lastname: Zhi
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.forename: Linjiao
authors.initials: L
authors.lastname: Jia
authors.forename: Chao
authors.initials: C
authors.lastname: Ding
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: You
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008727:Methotrexate / Q000494:pharmacology; D000089762:Multidrug Resistance-Associated Protein 2; D017239:Paclitaxel / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D000089762:Multidrug Resistance-Associated Protein 2; C578986:TUBB1 protein, human; C498585:TUBB3 protein, human; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate