Nguyen Mai Ly Thi, Bui Lan Anh, Pham Chi, Nham Phuong Linh Thi, Can VAN Mao, Doan Tran Duy Hai, Bozko Przemyslaw, Bui Khac Cuong, Nguyen Linh Toan
Department of Biochemistry, Military Hospital 103, Hanoi, Vietnam.
Laboratory Animal Research Center, Vietnam Military Medical University, Hanoi, Vietnam.
Anticancer Res. 2025 Jul;45(7):3059-3068. doi: 10.21873/anticanres.17670.
BACKGROUND/AIM: Colorectal cancer (CRC) was the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide in 2022. Despite advances in oncology, CRC prognosis and treatment outcomes have shown limited improvement over the past decades, highlighting the urgent need for more effective therapies. Adiponectin signaling, known for its tumor-suppressive role in various cancers including CRC, presents a promising therapeutic target. AdipoRon, an adiponectin receptor agonist, may offer a novel strategy by restoring this signaling pathway.
The anti-cancer effects of AdipoRon were evaluated using assays for cell viability, crystal violet staining, cell migration, apoptosis, and cell cycle distribution. Protein expression levels of AMPKα, phosphorylated AMPKα (pAMPKα), and STAT3 were assessed western blotting.
AdipoRon significantly inhibited HCT116 colorectal cancer cell proliferation under both low and high-density conditions in a dose-dependent manner. It also reduced cell migration. Treated cells exhibited an increased tendency toward apoptosis and a significant accumulation in the G phase of the cell cycle, accompanied by reduced proportions in the S and G/M phases. Furthermore, AdipoRon induced AMPKα phosphorylation and down-regulated the oncogenic protein STAT3.
AdipoRon effectively inhibited CRC cell proliferation and migration , effects that were associated with the up-regulation of the tumor suppressor protein pAMPKα and suppression of STAT3. These findings support the potential of AdipoRon as a promising therapeutic agent for CRC.
背景/目的：结直肠癌（CRC）是2022年全球第三大最常被诊断出的癌症，也是癌症相关死亡的第二大主要原因。尽管肿瘤学取得了进展，但在过去几十年中，CRC的预后和治疗效果改善有限，这凸显了对更有效治疗方法的迫切需求。脂联素信号传导在包括CRC在内的各种癌症中具有肿瘤抑制作用，是一个有前景的治疗靶点。AdipoRon是一种脂联素受体激动剂，可能通过恢复这一信号通路提供一种新策略。
通过细胞活力测定、结晶紫染色、细胞迁移、凋亡和细胞周期分布分析来评估AdipoRon的抗癌作用。采用蛋白质印迹法评估AMPKα、磷酸化AMPKα（pAMPKα）和STAT3的蛋白质表达水平。
AdipoRon在低密度和高密度条件下均以剂量依赖性方式显著抑制HCT116结肠癌细胞增殖。它还减少了细胞迁移。经处理的细胞凋亡倾向增加，细胞周期的G期显著积累，同时S期和G/M期的比例降低。此外，AdipoRon诱导AMPKα磷酸化并下调致癌蛋白STAT3。
AdipoRon有效抑制CRC细胞增殖和迁移，这些作用与肿瘤抑制蛋白pAMPKα的上调和STAT3的抑制有关。这些发现支持AdipoRon作为CRC有前景的治疗药物的潜力。
