Piperlongumine in combination with EGFR tyrosine kinase inhibitors for the treatment of lung cancer cells.

IF 2 4区 医学 Q3 ONCOLOGY Oncology Research Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI:10.32604/or.2024.053972
Shail Rakesh Modi, Terrick Andey
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引用次数: 0

Abstract

Objectives: EGFR tyrosine kinase inhibitor (EGFR-TKI) therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer (NSCLC). However, the high incidence of acquired resistance to these EGFR-TKIs may preclude their effectiveness. Piperlongumine (PPL), an extract from the long pepper fruit (Piper longum), has been shown to possess anticancer properties. The purpose of the study was to investigate piperlongumine as an anticancer agent and to study a combination treatment approach with EGFR-TKIs against lung cancer cells.

Methods: Anticancer efficacy of PPL, erlotinib (ERL), gefitinib (GEF), and cisplatin (CIS) were investigated in H1299 and H1975 cell lines. Cells were treated with PPL, ERL, GEF, and CIS alone, and in combination, cell viability was determined after 72 h. The mechanism of PPL-induced cytotoxicity was investigated via reactive oxygen species (ROS) induction, and apoptosis induction using acridine orange/ethidium bromide staining and flow cytometry. The effect of treatment on EGFR-mediated oncogenic signaling was investigated by immunoblotting for mitogenic and apoptotic markers.

Results: PPL exhibited a potent cytotoxic effect in H1299 and H1975 cells compared to ERL, GEF, and CIS. Combination treatments of PPL with GEF and ERL showed significant reductions in cancer cells compared to control in both cell lines, which were associated with apoptotic induction, but without significant ROS induction. Compared to control, PPL with GEF significantly increased apoptotic cell death in H1975as confirmed with flow cytometry. Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level.

Conclusion: PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations.

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哌隆单胺与表皮生长因子受体酪氨酸激酶抑制剂联合治疗肺癌细胞。
目的:表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)疗法(如厄洛替尼和吉非替尼)已被批准用于治疗非小细胞肺癌(NSCLC)。然而,这些表皮生长因子受体-TKIs的获得性耐药性发生率较高,可能会影响其疗效。从长胡椒果实(Piper longum)中提取的胡椒龙葵碱(Piperlongumine,PPL)已被证明具有抗癌特性。本研究的目的是将胡椒龙葵碱作为一种抗癌剂进行研究,并研究与表皮生长因子受体抑制剂(EGFR-TKIs)联合治疗肺癌细胞的方法:方法:在H1299和H1975细胞系中研究了PPL、厄洛替尼(ERL)、吉非替尼(GEF)和顺铂(CIS)的抗癌效果。采用吖啶橙/溴化乙锭染色法和流式细胞术,通过活性氧(ROS)诱导和细胞凋亡诱导研究了PPL诱导细胞毒性的机制。通过免疫印迹法检测有丝分裂和细胞凋亡标记物,研究治疗对表皮生长因子受体介导的致癌信号转导的影响:结果:与 ERL、GEF 和 CIS 相比,PPL 对 H1299 和 H1975 细胞具有强效细胞毒性作用。与对照组相比,PPL 与 GEF 和 ERL 的联合处理可显著减少两种细胞系的癌细胞数量,这与诱导细胞凋亡有关,但没有明显的 ROS 诱导。流式细胞术证实,与对照组相比,含有 GEF 的 PPL 能显著增加 H1975 细胞的凋亡。单独或联合使用 PPL 可在分子水平上诱导抗致病性和细胞凋亡反应:结论:PPL 可使肺癌细胞对表皮生长因子受体-TKI 敏感,并在低浓度下诱导有效的细胞毒性作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Oncology Research
Oncology Research 医学-肿瘤学
CiteScore
4.40
自引率
0.00%
发文量
56
审稿时长
3 months
期刊介绍: Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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