肿瘤细胞治疗研究
英文原题：Sestrin2 in cancer: a foe or a friend?
Sestrin2是一种保守的抗氧化剂、代谢调节剂，也是P53的下游因子。
Sestrin2是一种保守的抗氧化剂、代谢调节因子以及P53的下游分子。Sestrin2能够抑制氧化应激和炎症，从而预防癌症的发生和进展。然而，Sestrin2通过激活核因子E2相关因子2（Nrf2）来减轻严重的氧化应激，从而增强癌细胞的存活和化疗耐药性。Sestrin2抑制内质网应激并激活癌细胞中的自噬和凋亡。减轻内质网应激和增强自噬可阻碍癌症发展，但在特定条件下既可加速也可阻碍癌症进展。此外，Sestrin2可通过下调哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）和缺氧诱导因子1-α（HIF-1α）来强力抑制致癌信号通路。相反，Sestrin2降低T细胞和NK 细胞的细胞毒性活性，从而帮助肿瘤细胞免疫逃逸。Sestrin2可在葡萄糖或谷氨酰胺缺乏等应激条件下增强肿瘤细胞的存活能力。癌细胞还可以在化疗或放疗期间上调Sestrin2，以减轻严重的氧化应激和内质网应激、增强自噬并抵抗治疗。近期研究揭示Sestrin2参与多种类型人类癌症的发生和进展。Sestrin2的作用可能因肿瘤类型而异，例如，多项研究揭示Sestrin2对结直肠癌具有保护作用，而关于肺癌的结果则存在争议。此外，Sestrin2表达与多种类型人类癌症（如结直肠癌、肺癌和肝细胞癌）的转移和生存相关。针对Sestrin2的靶向治疗或通过非编码RNA递送和载体系统等新技术调控其表达，可能改善肿瘤化疗并克服化疗耐药、转移和免疫逃逸，这些应通过未来试验加以研究。
Sestrin2 is a conserved antioxidant, metabolism regulator, and downstream of P53. Sestrin2 can suppress oxidative stress and inflammation, thereby preventing the development and progression of cancer. However, Sestrin2 attenuates severe oxidative stress by activating nuclear factor erythroid 2-related factor 2 (Nrf2), thereby enhancing cancer cells survival and chemoresistance. Sestrin2 inhibits endoplasmic reticulum stress and activates autophagy and apoptosis in cancer cells. Attenuation of endoplasmic reticulum stress and augmentation of autophagy hinders cancer development but can either expedite or impede cancer progression under specific conditions. Furthermore, Sestrin2 can vigorously inhibit oncogenic signaling pathways through downregulation of mammalian target of rapamycin complex 1 (mTORC1) and hypoxia-inducible factor 1-alpha (HIF-1α). Conversely, Sestrin2 decreases the cytotoxic activity of T cells and natural killer cells which helps tumor cells immune evasion. Sestrin2 can enhance tumor cells viability in stress conditions such as glucose or glutamine deficiency. Cancer cells can also upregulate Sestrin2 during chemotherapy or radiotherapy to attenuate severe oxidative stress and ER stress, augment autophagy and resist the treatment. Recent studies unveiled that Sestrin2 is involved in the development and progression of several types of human cancer. The effect of Sestrin2 may differ depending on the type of tumor, for instance, several studies revealed that Sestrin2 protects against colorectal cancer, whereas results are controversial regarding lung cancer. Furthermore, Sestrin2 expression correlates with metastasis and survival in several types of human cancer such as colorectal cancer, lung cancer, and hepatocellular carcinoma. Targeted therapy for Sestrin2 or regulation of its expression by new techniques such as non-coding RNAs delivery and vector systems may improve cancer chemotherapy and overcome chemoresistance, metastasis and immune evasion that should be investigated by future trials.
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