Nishi Masaaki, Nakasu Chiharu, Yoshimoto Toshiaki, Tokunaga Takuya, Kashihara T Hideya, Takasu Chie, Ishikawa Daichi, Wada Yuma, Shimada Mitsuo
Department of Surgery, Institute of Biomedical Sciences Tokushima University Tokushima Japan.
Department of Community Medicine and Medical Science Tokushima University Tokushima Japan.
Ann Gastroenterol Surg. 2025 Feb 24;9(4):761-768. doi: 10.1002/ags3.70004. eCollection 2025 Jul.
The concepts examined in tumor metabolism research have been moving away from cancer cells themselves and the tumor microenvironment has become a focus of investigation. Epigenetic changes affecting glucose metabolism in cancer-associated fibroblasts (CAFs) in the tumor microenvironment regulate the malignancy of cancer cells. Light-emitting diode (LED) have several functional effects, including anti-tumor effects, through a variety of mechanisms. We previously reported that blue LED irradiation had an anti-tumor effect via Opsin 3 that suppress CAF function in vivo and in vitro. However, the detailed mechanism by which LED affect CAF regulation remained unclear.
CAFs were induced from human intestinal fibroblasts co-cultured with colon cancer cells. Using lactate assays and reverse transcription-quantitative PCR, the effects of LED irradiation on glycolysis in CAFs were investigated. The effects of LED irradiation for metabolic coupling were evaluated in vitro.
Reverse transcription-quantitative PCR showed higher expression of CAF marker genes in induced CAFs. Blue LED irradiation of induced CAFs suppressed their ability to promote characteristics of tumor malignancy of colon cancer cell line. LED treatment decreased expression of glycolysis markers, including phosphofructokinase and monocarboxylate transporter 4, indicating inhibition of glycolytic activity in CAFs. Extracellular secretion of lactate from CAFs was decreased by LED irradiation.
Blue LED irradiation targeted metabolic coupling between CAFs and colon cancer cells, thereby reducing the promotion of tumor progression by CAFs. Blue LED targeting glucose metabolism in CAFs is a promising anti-cancer treatment option.
肿瘤代谢研究中所探讨的概念已逐渐从癌细胞本身转移，肿瘤微环境已成为研究焦点。影响肿瘤微环境中癌症相关成纤维细胞（CAFs）葡萄糖代谢的表观遗传变化调节着癌细胞的恶性程度。发光二极管（LED）通过多种机制具有多种功能效应，包括抗肿瘤效应。我们之前报道过蓝色LED照射通过视蛋白3具有抗肿瘤作用，可在体内和体外抑制CAF功能。然而，LED影响CAF调节的详细机制仍不清楚。
从与结肠癌细胞共培养的人肠道成纤维细胞中诱导出CAFs。使用乳酸测定法和逆转录定量PCR，研究LED照射对CAFs糖酵解的影响。在体外评估LED照射对代谢偶联的影响。
逆转录定量PCR显示诱导的CAFs中CAF标记基因表达较高。对诱导的CAFs进行蓝色LED照射可抑制其促进结肠癌细胞系肿瘤恶性特征的能力。LED处理降低了包括磷酸果糖激酶和单羧酸转运蛋白4在内的糖酵解标志物的表达，表明抑制了CAFs中的糖酵解活性。LED照射降低了CAFs细胞外乳酸的分泌。
蓝色LED照射靶向CAFs与结肠癌细胞之间的代谢偶联，从而减少CAFs对肿瘤进展的促进作用。靶向CAFs葡萄糖代谢的蓝色LED是一种有前景的抗癌治疗选择。
