Liu Jun, Luo Dandong, Chen Xiaochuan, Liu Jiaqi, Chen Junxiong, Shi Mengchen, Dong Haiyan, Xu Yucheng, Wang Xinyou, Yu Zhaoliang, Liu Huanliang, Feng Yanchun
Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Department of General Surgery (Pancreatic Hepatobiliary Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, PR China.
Transl Oncol. 2025 Jan;51:102199. doi: 10.1016/j.tranon.2024.102199. Epub 2024 Dec 4.
The treatment of colorectal cancer (CRC) poses significant challenges in terms of drug resistance and poor prognosis, necessitating the exploration of effective therapeutic strategies. In this study, high-throughput drug screening was utilized to identify Chinese herbal medicines with notable therapeutic effects on CRC. Among the compounds identified, 4'-demethylpodophyllotoxin (DOP), a derivative of podophyllotoxin, emerged as a potent anti-cancer compound. DOP exhibited time- and dose-dependent growth inhibition on CRC cell lines and tumor organoids derived from patients. RNA-seq revealed that DOP activated the PI3K-AKT pathway, leading to tumor cell apoptosis and cell cycle arrest at the G2/M phase. Additionally, DOP induced DNA damage in CRC cells. To further validate its therapeutic efficacy in CRC, the DLD1-derived xenograft model demonstrated that DOP effectively suppressed CRC growth in vivo. In conclusion, these findings highlight the significant therapeutic potential of DOP as an anti-tumor drug for treating CRC, thereby opening new avenues for investigating Podophyllotoxin derivatives in this specific field.
结直肠癌（CRC）的治疗在耐药性和预后不良方面面临重大挑战，因此需要探索有效的治疗策略。在本研究中，利用高通量药物筛选来鉴定对CRC具有显著治疗效果的中药。在鉴定出的化合物中，鬼臼毒素衍生物4'-去甲基鬼臼毒素（DOP）成为一种有效的抗癌化合物。DOP对CRC细胞系和源自患者的肿瘤类器官表现出时间和剂量依赖性的生长抑制作用。RNA测序显示DOP激活PI3K-AKT通路，导致肿瘤细胞凋亡并使细胞周期停滞在G2/M期。此外，DOP诱导CRC细胞中的DNA损伤。为了进一步验证其在CRC中的治疗效果，DLD1衍生的异种移植模型表明DOP在体内有效抑制CRC生长。总之，这些发现突出了DOP作为治疗CRC的抗肿瘤药物的巨大治疗潜力，从而为在这一特定领域研究鬼臼毒素衍生物开辟了新途径。
