Jeong Ji Hye, Ryu Jae-Ha
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea.
Biomol Ther (Seoul). 2022 May 1;30(3):257-264. doi: 10.4062/biomolther.2022.008.
Colorectal cancer (CRC) is one of the most common malignant tumor. 5-FU is commonly used for the treatment of CRC. However, the development of drug resistance in tumor chemotherapy can seriously reduce therapeutic efficacy of 5-FU. Recent data show that FoxM1 is associated with 5-FU resistance in CRC. FoxM1 plays a critical role in the carcinogenesis and drug resistance of several malignancies. It has been reported that urushiol V isolated from the cortex of Stokes is cytotoxic to several types of cancer cells. However, the underlying molecular mechanisms for its antitumor activity and its potential to attenuate the chemotherapeutic resistance in CRC cells remain unknown. Here, we found that urushiol V could inhibit the cell proliferation and induced S-phase arrest of SW480 colon cancer cells. It inhibited protein expression level of FoxM1 through activation of AMPK. We also investigated the combined effect of urushiol V and 5-FU. The combination treatment reduced FoxM1 expression and consequently reduced cell growth and colony formation in 5-FU resistant colon cancer cells (SW480/5-FUR). Taken together, these result suggest that urushiol V from Stokes can suppress cell proliferation by inhibiting FoxM1 and enhance the antitumor capacity of 5-FU. Therefore, urushiol V may be a potential bioactive compound for CRC therapy.
结直肠癌（CRC）是最常见的恶性肿瘤之一。5-氟尿嘧啶（5-FU）常用于CRC的治疗。然而，肿瘤化疗中耐药性的产生会严重降低5-FU的治疗效果。最近的数据表明，叉头框蛋白M1（FoxM1）与CRC中的5-FU耐药性相关。FoxM1在几种恶性肿瘤的发生和耐药性中起关键作用。据报道，从漆树皮层分离出的漆酚V对几种类型的癌细胞具有细胞毒性。然而，其抗肿瘤活性的潜在分子机制及其减弱CRC细胞化疗耐药性的潜力仍不清楚。在此，我们发现漆酚V可抑制SW480结肠癌细胞的增殖并诱导其S期阻滞。它通过激活腺苷酸活化蛋白激酶（AMPK）抑制FoxM1的蛋白表达水平。我们还研究了漆酚V与5-FU的联合作用。联合治疗降低了FoxM1的表达，从而减少了5-FU耐药结肠癌细胞（SW480/5-FUR）的细胞生长和集落形成。综上所述，这些结果表明，来自漆树的漆酚V可通过抑制FoxM1来抑制细胞增殖，并增强5-FU的抗肿瘤能力。因此，漆酚V可能是一种用于CRC治疗的潜在生物活性化合物。
