Du Xusheng, Li Dongfan, Wang Guanjie, Fan Yali, Li Namiao, Chai Lili, Li Guangshun, Li Jianying
Department of Respiratory, Affiliated Xi'an Central Hospital, The Medical School of Xi'an Jiaotong University, Xi'an, China.
Department of Oncology, Affiliated Xi'an Central Hospital, The Medical School of Xi'an Jiaotong University, Xi'an, China.
Ann Transl Med. 2021 Feb;9(4):355. doi: 10.21037/atm-20-7770.
Lung cancer affects approximately 9% of women and 17% of men worldwide, and has a mortality rate of 17%. Previously published studies have suggested that oxidative stress expansion can lead to lung cancer. The aim of the current study was to analyze the possible inhibitory pathway of atorvastatin against lung cancer cells in an model.
The cytotoxic effects of atorvastatin on lung cancer cell lines H460 and A549 were analyzed, as well as cell cycle arrest and cell morphology. Benzo(a)pyrene (BaP) was used for the induction of lung cancer in experimental rats, and atorvastatin (5, 10, and 20 mg/kg body weight) was used for treatment in a dose-dependent manner. Body weight and lung tumors were calculated at regular intervals. Antioxidants, pro-inflammatory cytokines, phase I and II antioxidant enzymes, polyamine enzymes, and apoptosis markers were determined at end of the experimental study.
Cell cycle arrest occurred at the G2/M phase after atorvastatin treatment. Atorvastatin increased cytochrome C expression and caspase activity in a dose-dependent manner, and increased the activity of antioxidative enzymes, such as GPx, SOD, GST, reduced glutathione, and catalase, and reduced the level of nitrate and LPO. It also altered the xanthine oxidase (XO), Lactic Acid Dehydrogenase (LDH), quinone reductase (QR), UDP-glucuronosyltransferase (UDP-GT), adenosine deaminase (ADA), Aryl hydrocarbon hydroxylase (AHH), 5'-nucleotidase, cytochrome P450, cytochrome B5 and NADPH cytochrome C reductase levels. Atorvastatin was found to modulate polyamine enzyme levels, such as histamine, spermine, spermidine, and putrescine, and significantly (P<0.001) reduced the pro-inflammatory cytokine levels, such as tumor necrosis factor-α. Interleukin (IL)-6 and interleukin-1β (IL-1β) increased caspase-3 and caspase-9 levels in a dose-dependent manner.
Our findings indicate that atorvastatin can inhibit lung cancer through apoptosis.
肺癌在全球约影响9%的女性和17%的男性，死亡率为17%。先前发表的研究表明氧化应激扩大可导致肺癌。本研究的目的是在一个模型中分析阿托伐他汀对肺癌细胞的可能抑制途径。
分析阿托伐他汀对肺癌细胞系H460和A549的细胞毒性作用，以及细胞周期阻滞和细胞形态。苯并(a)芘（BaP）用于在实验大鼠中诱导肺癌，阿托伐他汀（5、10和20mg/kg体重）以剂量依赖方式用于治疗。定期计算体重和肺肿瘤。在实验研究结束时测定抗氧化剂、促炎细胞因子、I相和II相抗氧化酶、多胺酶和凋亡标志物。
阿托伐他汀治疗后细胞周期阻滞发生在G2/M期。阿托伐他汀以剂量依赖方式增加细胞色素C表达和半胱天冬酶活性，并增加抗氧化酶如谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）、谷胱甘肽S-转移酶（GST）、还原型谷胱甘肽和过氧化氢酶的活性，并降低硝酸盐和脂质过氧化物（LPO）水平。它还改变了黄嘌呤氧化酶（XO）、乳酸脱氢酶（LDH）、醌还原酶（QR）、尿苷二磷酸葡萄糖醛酸基转移酶（UDP-GT）、腺苷脱氨酶（ADA）、芳烃羟化酶（AHH）、5'-核苷酸酶、细胞色素P450、细胞色素B5和NADPH细胞色素C还原酶水平。发现阿托伐他汀可调节多胺酶水平，如组胺、精胺、亚精胺和腐胺，并显著（P<0.001）降低促炎细胞因子水平，如肿瘤坏死因子-α。白细胞介素（IL）-6和白细胞介素-1β（IL-1β）以剂量依赖方式增加半胱天冬酶-3和半胱天冬酶-9水平。
我们的研究结果表明阿托伐他汀可通过凋亡抑制肺癌。
