Gao Yanyan, Li Wei, Liu Xiaobo, Gao Fusheng, Zhao Xiaohua
Department of Internal Medicine, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
Department of Chest Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Mol Med Rep. 2015 Mar;11(3):2118-24. doi: 10.3892/mmr.2014.2936. Epub 2014 Nov 13.
Lung cancer is the primary malignancy of the lung and is the leading cause of cancer‑associated mortality in China. Multidrug resistance (MDR) is an essential aspect of lung cancer treatment failure and a popular topic of investigation in tumor studies. Previous studies have demonstrated that soluble resistance‑related calcium‑binding protein (Sorcin) is involved in the MDR of various types of human tumor, and that silencing Sorcin was able to reverse the MDR of several types of cultured human cancer cells. However, the effect and potential mechanism underlying the ability of Sorcin to reverse MDR in human lung cancer remains to be fully elucidated. The present study examined the role of Sorcin in the reversal of MDR in human lung cancer A549/DDP cells. The effects included increased drug sensitivity to cisplatin, apoptotic rate, cell cycle arrest in the G2/M phase and intracellular accumulation of rhodamine‑123, and decreased expression of multidrug resistance gene 1, lung resistance protein, multidrug resistance‑associated protein, glutathione S‑transferase π, ATP‑binding cassette transporter A2 (ABCA2), ABCA5, B‑cell lymphoma 2 and P‑glycoprotein, and the depletion of glutathione in Sorcin‑silenced A549/DDP cells. The present study also revealed that there was a downregulation of p‑Akt and phosphorylated extracellular signal‑regulated kinase (p‑ERK), and a decreased transcriptional activation of nuclear factor κB, signal transducer and activator of transcription (STAT)3, STAT5 and nuclear factor of activated T‑cells following silencing of Sorcin. The results indicated that Sorcin may be used as a potential therapeutic target for MDR through inhibiting the Akt and ERK pathways in human lung cancer.
肺癌是肺部的原发性恶性肿瘤，是中国癌症相关死亡的主要原因。多药耐药（MDR）是肺癌治疗失败的一个重要方面，也是肿瘤研究中一个热门的研究课题。先前的研究表明，可溶性耐药相关钙结合蛋白（Sorcin）参与了多种类型人类肿瘤的多药耐药，并且沉默Sorcin能够逆转几种培养的人类癌细胞的多药耐药。然而，Sorcin逆转人类肺癌多药耐药的作用及潜在机制仍有待充分阐明。本研究检测了Sorcin在逆转人肺癌A549/DDP细胞多药耐药中的作用。其作用包括增加对顺铂的药物敏感性、凋亡率、使细胞周期停滞于G2/M期以及罗丹明-123在细胞内的蓄积，并降低多药耐药基因1、肺耐药蛋白、多药耐药相关蛋白、谷胱甘肽S-转移酶π、ATP结合盒转运体A2（ABCA2）、ABCA5、B细胞淋巴瘤2和P-糖蛋白的表达，以及沉默Sorcin的A549/DDP细胞中谷胱甘肽的消耗。本研究还发现，沉默Sorcin后，p-Akt和磷酸化细胞外信号调节激酶（p-ERK）下调，核因子κB、信号转导和转录激活因子（STAT）3、STAT5以及活化T细胞核因子的转录激活降低。结果表明，Sorcin可能通过抑制人肺癌中的Akt和ERK途径作为多药耐药的潜在治疗靶点。
