Wu Xiao-Yu, Xu Wen-Wen, Huan Xiang-Kun, Wu Guan-Nan, Li Gang, Zhou Yu-Hong, Najafi Masoud
Department of Surgical Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.
Department of Gynaecology, The Affiliated Hospital of Nanjing University of Chinese Medi-Cine, Nanjing, 210029, Jiangsu, China.
Mol Cell Biochem. 2023 Jan;478(1):197-214. doi: 10.1007/s11010-022-04502-4. Epub 2022 Jun 30.
Cancer resistance to anti-tumour agents has been one of the serious challenges in different types of cancer treatment. Usually, an increase in the cell death markers can predict a higher rate of survival among patients diagnosed with cancer. By increasing the regulation of survival genes, cancer cells can display a higher resistance to therapy through the suppression of anti-tumour immunity and inhibition of cell death signalling pathways. Administration of certain adjuvants may be useful in order to increase the therapeutic efficiency of anti-cancer therapy through the stimulation of different cell death pathways. Several studies have demonstrated that metformin, an antidiabetic drug with anti-cancer properties, amplifies cell death mechanisms, especially apoptosis in a broad-spectrum of cancer cells. Stimulation of the immune system by metformin has been shown to play a key role in the induction of cell death. It seems that the induction or suppression of different cell death mechanisms has a pivotal role in either sensitization or resistance of cancer cells to therapy. This review explains the cellular and molecular mechanisms of cell death following anticancer therapy. Then, we discuss the modulatory roles of metformin on different cancer cell death pathways including apoptosis, mitotic catastrophe, senescence, autophagy, ferroptosis and pyroptosis.
癌症对抗肿瘤药物的耐药性一直是各类癌症治疗中的严峻挑战之一。通常，细胞死亡标志物的增加可预示癌症确诊患者的较高生存率。通过增强生存基因的调控，癌细胞可通过抑制抗肿瘤免疫和抑制细胞死亡信号通路来表现出对治疗的更高耐药性。为了通过刺激不同的细胞死亡途径提高抗癌治疗的疗效，给予某些佐剂可能会有所帮助。多项研究表明，二甲双胍作为一种具有抗癌特性的抗糖尿病药物，可放大细胞死亡机制，尤其是在广谱癌细胞中的细胞凋亡。二甲双胍对免疫系统的刺激已被证明在诱导细胞死亡中起关键作用。不同细胞死亡机制的诱导或抑制似乎在癌细胞对治疗的致敏或耐药中起关键作用。本综述解释了抗癌治疗后细胞死亡的细胞和分子机制。然后，我们讨论二甲双胍对不同癌细胞死亡途径的调节作用，包括细胞凋亡、有丝分裂灾难、衰老、自噬、铁死亡和焦亡。
