Li Bingru, Allela Omer Qutaiba B, Alkhazali Wadhah Hasan, Vadia Nasir, Renuka Jyothi S, Panigrahi Rajashree, Chauhan Ashish Singh, Singh Surbhi, Akhrorova Malika, Sameer Hayder Naji, Yaseen Ahmed, Athab Zainab H, Adil Mohaned
Yunnan Medical Health College, Kunming, 650032, Yunnan, China.
College of Pharmacy, Alnoor University, Mosul, Iraq.
Med Oncol. 2025 Jul 13;42(8):329. doi: 10.1007/s12032-025-02903-1.
Oral cancer remains a major global health challenge due to its aggressive nature, high recurrence rates, and limited treatment options. Resveratrol (RV), a naturally occurring polyphenol, has demonstrated promising anticancer properties in various malignancies, including oral cancer. This systematic review aimed to evaluate preclinical evidence on RV's therapeutic effects in oral cancer, focusing on its mechanisms of apoptosis induction, metastasis inhibition, autophagy regulation, and immune modulation.
A systematic review was conducted following PRISMA guidelines, with a comprehensive search in Google Scholar, PubMed, Embase, Scopus, and Web of Science for preclinical studies published up to March 2, 2025. Both in vitro and in vivo studies investigating RV's effects on oral cancer were included based on predefined inclusion and exclusion criteria. Data extraction was performed independently by multiple researchers, with discrepancies resolved through consensus. Key mechanisms of RV's anticancer activity, including apoptosis, metastasis suppression, autophagy, and immune regulation, were analyzed.
Out of 346 studies screened, 19 (four in vivo and 15 in vitro) met the eligibility criteria. RV exhibited potent anticancer effects in a dose- and time-dependent manner, significantly reducing oral cancer cell viability and tumor growth in animal models. Mechanistically, RV induced apoptosis through caspase-3, -7, and -9 activation and modulation of pro-apoptotic (Bax, Bak) and anti-apoptotic (Bcl-2, Bcl-XL) proteins. RV also inhibited key oncogenic pathways, including Akt/mTOR and JAK2/STAT3, thereby suppressing tumor proliferation and immune evasion. Additionally, RV impaired metastatic progression by downregulating EMT-related transcription factors (TWIST, SLUG, and Zeb1) and reducing angiogenic markers such as VEGF and MMPs. Notably, RV induced autophagy in a dose- and time-dependent manner, as evidenced by increased LC3-II, Beclin1, and p62 expression. In cisplatin-resistant oral cancer models, RV promoted both apoptotic and autophagic cell death, suggesting its potential as an adjuvant therapy.
This systematic review underscored the potential of RV as a promising anticancer agent for oral cancer. Through apoptosis induction, metastasis suppression, autophagy modulation, and immune regulation, RV demonstrated broad-spectrum anticancer effects. However, its low bioavailability remains a significant challenge. Future research should focus on optimizing drug delivery strategies, such as nanoparticle formulations and combination therapies, to enhance RV's therapeutic efficacy and facilitate clinical translation.
口腔癌因其侵袭性、高复发率和有限的治疗选择，仍然是一项重大的全球健康挑战。白藜芦醇（RV）是一种天然存在的多酚，已在包括口腔癌在内的各种恶性肿瘤中显示出有前景的抗癌特性。本系统评价旨在评估关于RV对口腔癌治疗效果的临床前证据，重点关注其诱导凋亡、抑制转移、调节自噬和免疫调节的机制。
按照PRISMA指南进行系统评价，在谷歌学术、PubMed、Embase、Scopus和科学网中全面检索截至2025年3月2日发表的临床前研究。根据预定义的纳入和排除标准，纳入研究RV对口腔癌影响的体外和体内研究。由多名研究人员独立进行数据提取，通过共识解决差异。分析了RV抗癌活性的关键机制，包括凋亡、转移抑制、自噬和免疫调节。
在筛选的346项研究中，19项（4项体内研究和15项体外研究）符合纳入标准。RV以剂量和时间依赖性方式表现出强大的抗癌作用，在动物模型中显著降低口腔癌细胞活力和肿瘤生长。从机制上讲，RV通过激活半胱天冬酶-3、-7和-9以及调节促凋亡蛋白（Bax、Bak）和抗凋亡蛋白（Bcl-2、Bcl-XL）诱导凋亡。RV还抑制关键的致癌途径，包括Akt/mTOR和JAK2/STAT3，从而抑制肿瘤增殖和免疫逃逸。此外，RV通过下调与上皮-间质转化（EMT）相关的转录因子（TWIST、SLUG和Zeb1）并减少血管生成标志物如血管内皮生长因子（VEGF）和基质金属蛋白酶（MMPs）来损害转移进程。值得注意的是，RV以剂量和时间依赖性方式诱导自噬，LC3-II、Beclin1和p62表达增加证明了这一点。在顺铂耐药的口腔癌模型中，RV促进凋亡和自噬性细胞死亡，表明其作为辅助治疗的潜力。
本系统评价强调了RV作为一种有前景的口腔癌抗癌药物的潜力。通过诱导凋亡、抑制转移、调节自噬和免疫调节，RV显示出广谱抗癌作用。然而，其低生物利用度仍然是一个重大挑战。未来的研究应专注于优化药物递送策略，如纳米颗粒制剂和联合疗法，以提高RV的治疗效果并促进临床转化。
