The emergence of multi drug resistance in non-small cell lung cancer (NSCLC) patients is a major challenge towards the efficacy of chemotherapy. Thus, there is an urgent need for the newer, better clinically targeted strategies to treat this disease. Earlier studies from our laboratory revealed the apoptotic activity of Maackia amurensis agglutinin (MAA) in human NSCLC cells. In this study, the effect of MAA on drug resistant NSCLC cells was investigated. Two Paclitaxel-resistant NSCLC sub-lines (A549/PTX100 and NCI-H460/PTX100) were developed from A549 & NCI-H460 cell lines respectively. The generation of drug resistance phenotype was confirmed by the expression of cell surface MDR-1. Both the drug resistant sub-lines showed distinct morphological alterations. MAA interacted with the cell-surface protein(s) of apparent M_r ~66 kDa and induced apoptosis in both the sub-lines through intrinsic/mitochondrial pathway, involving reduction in mitochondrial trans-membrane potential, up-regulation of Bax, unaltered/decreased expression of Bcl-X_L, release of mitochondrial cytochrome c into the cytosol and activation of pro-caspases (−9&-3). Our findings highlighted the potential of this plant agglutinin to serve as an apoptosis inducing agent in drug resistant NSCLC cells.

中文翻译：

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ack果凝集素诱导培养的耐药性人非小细胞肺癌细胞凋亡。

非小细胞肺癌（NSCLC）患者中多药耐药的出现是对化疗功效的重大挑战。因此，迫切需要更新，更好的临床靶向策略来治疗该疾病。我们实验室的早期研究表明，黑毛黑麦（Maackia amurensis）的凋亡活性人NSCLC细胞中的凝集素（MAA）。在这项研究中，研究了MAA对耐药NSCLC细胞的作用。从A549和NCI-H460细胞系分别开发了两个耐紫杉醇的NSCLC子系（A549 / PTX100和NCI-H460 / PTX100）。通过细胞表面MDR-1的表达证实了耐药性表型的产生。两种耐药亚系均表现出明显的形态学改变。MAA相互作用与细胞表面蛋白表观M的（S）_{- [R}通过固有/线粒体途径在两个子行〜66 kDa的和诱导细胞凋亡，涉及线粒体跨膜电位减少，Bax表达的上调，不变/ Bcl-X _L表达降低，将线粒体细胞色素c释放到细胞质中并激活前胱天蛋白酶（-9＆-3）。我们的发现突出了这种植物凝集素在耐药性NSCLC细胞中作为凋亡诱导剂的潜力。