An JaeJin, Ha Eun-Mi
Medical Convergence Textile Center, Gyeongbuk Technopark, Gyeongsangbuk-do 38412, Republic of Korea.
Department of Pharmacology, College of Pharmacy, Catholic University of Daegu 38430, Republic of Korea.
J Microbiol Biotechnol. 2016 Aug 28;26(8):1490-503. doi: 10.4014/jmb.1605.05024.
Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors. The human gastrointestinal tract contains a complex gut microbiota that is essential for the host's homeostasis. Recently, many studies have reported correlations between gut flora and the onset, progression, and treatment of CRC. The present study confirms that the most representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN), selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT- 116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced an anticancer mechanism by inactivating the Wnt/β-catenin signaling of chemoresistant CRC cells, and reducing the formation and size of colonospheres. In conclusion, our results show that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal cancer stem-like cells by reversing the development of resistance to anticancer drugs. This implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for chemoresistant CRC.
结直肠癌（CRC）是全球第三大常见癌症。尽管5-氟尿嘧啶（5-FU）是结直肠癌的代表性化疗药物，但由于其耐药特性，存在治疗局限性。结直肠癌细胞可发展为具有自我更新潜能的癌症干细胞（CSCs），从而引发恶性肿瘤。人类胃肠道含有复杂的肠道微生物群，对宿主的内环境稳定至关重要。最近，许多研究报道了肠道菌群与结直肠癌的发生、发展及治疗之间的相关性。本研究证实，人类最具代表性的共生细菌植物乳杆菌（LP）的上清液（SN）可选择性抑制5-FU耐药结直肠癌细胞（HT-29和HCT-116）的特性。LP SN抑制了CSCs特异性标志物CD44、133、166和ALDH1的表达。LP SN与5-FU联合治疗可抑制结直肠癌细胞的存活，并通过诱导caspase-3活性导致细胞死亡。LP SN与5-FU联合治疗通过使耐药结直肠癌细胞的Wnt/β-连环蛋白信号失活，以及减少结肠球的形成和大小，诱导了抗癌机制。总之，我们的结果表明，LP SN可增强5-FU对结肠癌的治疗效果，并通过逆转对抗癌药物的耐药性发展来减少结直肠癌干细胞样细胞。这意味着益生菌物质作为耐药性结直肠癌的生物治疗药物可能是有用的治疗选择。
