Ma Chong, Yin Jingyi, Feng Xiao, Wang Xin, Cao Xiaodie, Zhang Chen, Cui Rongjie, Wei Jingru, He Xu, Li Yan, Chen Li
Department of Pathophysiology, School of Basic Medicine, Kunming University of Science and Technology, Kunming, China.
The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Heliyon. 2024 Aug 9;10(16):e36032. doi: 10.1016/j.heliyon.2024.e36032. eCollection 2024 Aug 30.
Non-small cell lung cancer (NSCLC) is associated with high mortality and morbidity rates. Despite major progress of treatment of NSCLC over the past few decades, the prognosis of advanced NSCLC is poor, with 5-year survival rates ranging from 2 % to 13 %. is a traditional Chinese medicine used to promote blood circulation, reduce swelling, heal ulcers, disperse lumps and tumors, and resolve blood stasis. In the present study, the anti-proliferative and pro-apoptotic effects and potential mechanisms of action of extract (BCE) in SPC-A1 and NCI-H460 NSCLC cells were investigated using MTS, flow cytometry, and western blotting. Also, xenograft model was established to investigate the anti-NSCLC effects of BCE. The compounds in BCE were quantified using gas chromatography-mass spectrometry (GC-MS). Twenty compounds were found in BCE, and BCE induced cell cycle arrest significantly inhibited the proliferation of NSCLC. Furthermore, BCE was found to induce Cyto C release and the activation of Caspase-3, -8, -9, PARP, ultimately inducing apoptosis in NSCLC cells through both exogenous and endogenous apoptotic pathways (the mitochondrial pathway). BCE also blocked the MAPK (Ras/Raf) and Akt signaling pathways, significantly downregulating the expression of Ras, Raf, Erk1/2, p-Erk1/2, Akt, and p-Akt proteins. Furthermore, BCE significantly inhibited the growth of NSCLC cells SPC-A1 in nude mice and downregulated Ras, Raf, Akt, and p-Akt expression . The antitumor effects of BCE suggest its potential clinical application in patients with NSCLC, especially in those bearing Ras or Raf mutations.
非小细胞肺癌(NSCLC)的死亡率和发病率都很高。尽管在过去几十年里NSCLC的治疗取得了重大进展,但晚期NSCLC的预后仍然很差,5年生存率在2%至13%之间。[某种中药名称]是一种传统中药,用于促进血液循环、消肿、愈合溃疡、消散肿块和肿瘤以及活血化瘀。在本研究中,使用MTS、流式细胞术和蛋白质免疫印迹法研究了[中药名称]提取物(BCE)对SPC-A1和NCI-H460 NSCLC细胞的抗增殖和促凋亡作用及其潜在作用机制。此外,还建立了异种移植模型来研究BCE的抗NSCLC作用。使用气相色谱-质谱联用仪(GC-MS)对BCE中的化合物进行定量分析。在BCE中发现了20种化合物,BCE诱导细胞周期停滞,显著抑制NSCLC的增殖。此外,发现BCE可诱导细胞色素C释放以及半胱天冬酶-3、-8、-9、聚(二磷酸腺苷-核糖)聚合酶(PARP)的激活,最终通过外源性和内源性凋亡途径(线粒体途径)诱导NSCLC细胞凋亡。BCE还阻断丝裂原活化蛋白激酶(MAPK,Ras/Raf)和Akt信号通路,显著下调Ras、Raf、细胞外信号调节激酶1/2(Erk1/2)、磷酸化细胞外信号调节激酶1/2(p-Erk1/2)、Akt和磷酸化Akt蛋白的表达。此外,BCE显著抑制裸鼠体内NSCLC细胞SPC-A1的生长,并下调Ras、Raf、Akt和p-Akt的表达。BCE的抗肿瘤作用表明其在NSCLC患者中具有潜在的临床应用价值,尤其是在那些携带Ras或Raf突变的患者中。