Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Faculty of Medicine, Islamic Azad University Tonekabon Branch, Tonekabon, Iran.
Environ Res. 2023 Sep 15;233:116458. doi: 10.1016/j.envres.2023.116458. Epub 2023 Jun 20.
Colorectal cancer (CRC) ranks as the third most aggressive tumor globally, and it can be categorized into two forms: colitis-mediated CRC and sporadic CRC. The therapeutic approaches for CRC encompass surgical intervention, chemotherapy, and radiotherapy. However, even with the implementation of these techniques, the 5-year survival rate for metastatic CRC remains at a mere 12-14%. In the realm of CRC treatment, gene therapy has emerged as a novel therapeutic approach. Among the crucial molecular pathways that govern tumorigenesis, STAT3 plays a significant role. This pathway is subject to regulation by cytokines and growth factors. Once translocated into the nucleus, STAT3 influences the expression levels of factors associated with cell proliferation and metastasis. Literature suggests that the upregulation of STAT3 expression is observed as CRC cells progress towards metastatic stages. Consequently, elevated STAT3 levels serve as a significant determinant of poor prognosis and can be utilized as a diagnostic factor for cancer patients. The biological and malignant characteristics of CRC cells contribute to low survival rates in patients, as the upregulation of STAT3 prevents apoptosis and promotes pro-survival autophagy, thereby accelerating tumorigenesis. Furthermore, STAT3 plays a role in facilitating the proliferation of CRC cells through the stimulation of glycolysis and promoting metastasis via the induction of epithelial-mesenchymal transition (EMT). Notably, an intriguing observation is that the upregulation of STAT3 can mediate resistance to 5-fluorouracil, oxaliplatin, and other anti-cancer drugs. Moreover, the radio-sensitivity of CRC diminishes with increased STAT3 expression. Compounds such as curcumin, epigallocatechin gallate, and other anti-tumor agents exhibit the ability to suppress STAT3 and its associated pathways, thereby impeding tumorigenesis in CRC. Furthermore, it is worth noting that nanostructures have demonstrated anti-proliferative and anti-metastatic properties in CRC.
结直肠癌（CRC）是全球第三大侵袭性肿瘤，可分为炎症相关性 CRC 和散发性 CRC。CRC 的治疗方法包括手术干预、化疗和放疗。然而，即使采用这些技术，转移性 CRC 的 5 年生存率仍仅为 12-14%。在 CRC 治疗中，基因治疗已成为一种新的治疗方法。在调控肿瘤发生的关键分子途径中，STAT3 发挥着重要作用。该途径受细胞因子和生长因子的调节。一旦转位到细胞核内，STAT3 就会影响与细胞增殖和转移相关的因子的表达水平。文献表明，STAT3 表达的上调在 CRC 细胞向转移性阶段进展时观察到。因此，STAT3 水平的升高是预后不良的重要决定因素，可作为癌症患者的诊断因素。CRC 细胞的生物学和恶性特征导致患者的生存率较低，因为 STAT3 的上调阻止了细胞凋亡并促进了促进生存的自噬，从而加速了肿瘤的发生。此外，STAT3 通过刺激糖酵解促进 CRC 细胞的增殖，并通过诱导上皮-间充质转化（EMT）促进转移。值得注意的是，一个有趣的观察结果是，STAT3 的上调可以介导对 5-氟尿嘧啶、奥沙利铂和其他抗癌药物的耐药性。此外，CRC 的放射敏感性随着 STAT3 表达的增加而降低。姜黄素、表没食子儿茶素没食子酸酯和其他抗肿瘤药物等化合物能够抑制 STAT3 及其相关途径，从而阻止 CRC 中的肿瘤发生。此外，值得注意的是，纳米结构在 CRC 中表现出抗增殖和抗转移的特性。
