Wen Chuangyu, Huang Lanlan, Chen Junxiong, Lin Mengmeng, Li Wen, Lu Biyan, Rutnam Zina Jeyapalan, Iwamoto Aikichi, Wang Zhongyang, Yang Xiangling, Liu Huanliang
Guangdong Institute of Gastroenterology and the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China.
Guangdong Provincial Key Laboratory of Allergy and Immunology, Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China.
Int J Oncol. 2015 Nov;47(5):1663-71. doi: 10.3892/ijo.2015.3166. Epub 2015 Sep 15.
The emergence of chemoresistance is a major limitation of colorectal cancer (CRC) therapies and novel biologically based therapies are urgently needed. Natural products represent a novel potential anticancer therapy. Gambogic acid (GA), a small molecule derived from Garcinia hanburyi Hook. f., has been demonstrated to be highly cytotoxic to several types of cancer cells and have low toxicity to the hematopoietic system. However, the potential role of GA in colorectal cancer and its ability to overcome the chemotherapeutic resistance in CRC cells have not been well studied. In the present study, we showed that GA directly inhibited proliferation and induced apoptosis in both 5-fluorouracil (5-FU) sensitive and 5-FU resistant colorectal cancer cells; induced apoptosis via activating JNK signaling pathway. The data, therefore, suggested an alternative strategy to overcome 5-FU resistance in CRC and that GA could be a promising medicinal compound for colorectal cancer therapy.
化疗耐药性的出现是结直肠癌（CRC）治疗的主要限制因素，因此迫切需要新型的基于生物学的治疗方法。天然产物代表了一种新型的潜在抗癌疗法。藤黄酸（GA）是一种从藤黄属植物中提取的小分子化合物，已被证明对多种癌细胞具有高度细胞毒性，而对造血系统毒性较低。然而，GA在结直肠癌中的潜在作用及其克服CRC细胞化疗耐药性的能力尚未得到充分研究。在本研究中，我们发现GA直接抑制5-氟尿嘧啶（5-FU）敏感和5-FU耐药的结直肠癌细胞的增殖并诱导其凋亡；通过激活JNK信号通路诱导细胞凋亡。因此，这些数据提示了一种克服CRC中5-FU耐药性的替代策略，并且GA可能是一种有前途的用于结直肠癌治疗的药用化合物。
