title: Overcoming paclitaxel resistance in lung cancer cells via dual inhibition of stathmin and Bcl-2.
abstract: Lung cancer is the leading cause of death from malignancy in people and over 85% of these patients eventually die from disseminated disease. Paclitaxel (TAX) is widely used as an antimicrotubule agent for the treatment of lung cancer. Unfortunately, the resistance to this antimicrotubule agent occurs frequently. Stathmin (STMN1) is a ubiquitous microtubule destabilizing protein linked to cancer and cell health and its expression level often correlates with cancer stage progression and prognosis for survival. Overexpression of the antiapoptotic protein Bcl-2 has been shown to prolong drug-induced growth arrest, potentially inducing resistance. In this study, we used a short hairpin RNA (shRNA) approach to evaluate the effect of STMN1 and Bcl-2 downregulation in the sensitivity to TAX in lung cancer cells. We achieved significant downregulation of STMN1 and Bcl-2 mRNA and protein expression by a combination of double shRNA treatment strategy. Our experimental data showed that inhibition of STMN1 and Bcl-2 expression with RNA interference can sensitize lung cancer cells to TAX. These findings suggest a novel approach to improve the efficacy of certain antimicrotubule agents against lung cancer by regulating the function of STMN1 and Bcl-2.
authors.affiliation: The First Clinical Medical College, Nanjing Medical University, Nanjing, China.
authors.forename: Zheng-Xiang
authors.initials: ZX
authors.lastname: Han
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wang
authors.forename: Guan
authors.initials: G
authors.lastname: Jiang
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Du
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Gao
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Pei
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C493995:STMN1 protein, human; D050777:Stathmin; D017239:Paclitaxel