Abstract LB073: The growth inhibitory effect of paclitaxel on gefitinib-resistant non-small cell lung cancer (NSCLC) cells during the COVID-19 pandemic

Mohiuddin, H. Kimura, T. Sone, S. Watanabe, Hiroki Matsuoka, K. Saeki, Nanao Terada, M. Abo, K. Kasahara
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Abstract

Background: Coronavirus disease 2019 (COVID-19) has posed a great challenge for the treatment of cancer patients. COVID-19 presents as a severe respiratory infection in aging individuals, including lung cancer patients. COVID-19 may be linked to the progression of aggressive lung cancer. Conversely, the side effects of chemotherapy, such as chemotherapy resistance and the acceleration of cellular senescence could worsen COVID-19. Considering the above-mentioned facts, our present work aimed to investigate the role of paclitaxel (a chemotherapy drug) in the cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant NSCLC cells (PC9-MET) and to reveal the underlying mechanisms. Methods: PC9-MET cells were treated with paclitaxel for 72 h and were then evaluated by a cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, ROS assay, SA-β-Gal staining, TUNEL assay and Western blotting.Results: Our results revealed that paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Additionally, paclitaxel increased ROS production, leading to DNA damage. Importantly, paclitaxel eliminated cellular senescence, which was observed by SA-β-Gal staining.Conclusion: In light of these findings, paclitaxel could be a promising anticancer drug and could offer a new therapeutic strategy for gefitinib-resistant NSCLC during the COVID-19 pandemic. Citation Format: Md Mohiuddin, Hideharu Kimura, Takashi Sone, Satoshi Watanabe, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Miki Abo, Kazuo Kasahara. The growth inhibitory effect of paclitaxel on gefitinib-resistant non-small cell lung cancer (NSCLC) cells during the COVID-19 pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB073.
摘要:2019冠状病毒病疫情期间紫杉醇对吉非替尼耐药非小细胞肺癌(NSCLC)细胞的生长抑制作用
背景:2019冠状病毒病(COVID-19)对癌症患者的治疗提出了巨大挑战。COVID-19在包括肺癌患者在内的老年人中表现为严重的呼吸道感染。COVID-19可能与侵袭性肺癌的进展有关。相反,化疗的副作用,如化疗耐药性和细胞衰老加速,可能会加重COVID-19。考虑到上述事实,本研究旨在探讨紫杉醇(一种化疗药物)在吉非替尼耐药NSCLC细胞(PC9-MET)增殖、凋亡和细胞衰老中的作用,并揭示其潜在机制。方法:采用紫杉醇处理PC9-MET细胞72 h,采用细胞活力测定、DAPI染色、Giemsa染色、凋亡测定、ROS测定、SA-β-Gal染色、TUNEL染色、Western blot检测。结果:紫杉醇显著降低PC9-MET细胞活力,诱导细胞凋亡形态学特征。通过增加caspase-3、caspase-9和PARP的表达来观察紫杉醇的凋亡作用。此外,紫杉醇增加ROS的产生,导致DNA损伤。重要的是,紫杉醇可以消除细胞衰老,SA-β-Gal染色观察到这一点。结论:鉴于这些发现,紫杉醇可能是一种有前景的抗癌药物,并可能在COVID-19大流行期间为吉非替尼耐药NSCLC提供新的治疗策略。引用格式:Md Mohiuddin, Hideharu Kimura, Takashi Sone, Satoshi Watanabe, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Miki Abo, Kazuo Kasahara。2019冠状病毒病疫情期间紫杉醇对吉非替尼耐药非小细胞肺癌(NSCLC)细胞的生长抑制作用[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要nr LB073。
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