The First Clinical Medical College, Nanjing Medical University, Nanjing, China.
Cancer Biother Radiopharm. 2013 Jun;28(5):398-405. doi: 10.1089/cbr.2012.1323. Epub 2013 Mar 15.
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.
肺癌是导致人类恶性肿瘤死亡的主要原因，超过 85%的此类患者最终死于转移性疾病。紫杉醇（TAX）被广泛用作治疗肺癌的抗微管剂。不幸的是，这种抗微管剂经常产生耐药性。Stathmin（STMN1）是一种普遍存在的微管不稳定蛋白，与癌症和细胞健康有关，其表达水平通常与癌症分期进展和生存预后相关。抗凋亡蛋白 Bcl-2 的过表达已被证明可延长药物诱导的生长停滞，从而可能诱导耐药性。在这项研究中，我们使用短发夹 RNA（shRNA）方法来评估 STMN1 和 Bcl-2 下调对肺癌细胞对 TAX 敏感性的影响。我们通过双重 shRNA 治疗策略实现了 STMN1 和 Bcl-2 mRNA 和蛋白表达的显著下调。我们的实验数据表明，用 RNA 干扰抑制 STMN1 和 Bcl-2 的表达可以使肺癌细胞对 TAX 敏感。这些发现表明，通过调节 STMN1 和 Bcl-2 的功能，为提高某些抗微管剂治疗肺癌的疗效提供了一种新方法。
