Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis.
Gastric carcinoma (GC) is the second leading cause of cancer-related mortality worldwide. The efficacy of standard chemotherapy for GC, such as cisplatin (CDDP), is dissatisfactory partly due to the toxic/side-effects. Sulforaphane (SFN), which exhibits effective anti-cancer functions, is a phytochemical converted from cruciferous plants. Our present study aimed to identify whether SFN could enhance the anti-cancer effects of low-dose CDDP and to determine the underlying mechanisms. Herein, co-exposure of SFN and CDDP significantly inhibited the viabilities of gastric cancer cells. For the molecular mechanisms, CDDP alone increased the cancer stem cell (CSC)-like properties in gastric cancer cells via activating the interleukin-6 (IL-6)/IL-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signaling. However, SFN could activate the microRNA-124 (miR-124), which directly targets the 3'-untranslated regions (UTR) of the IL-6R and STAT3. Moreover, knockdown of miR-124 eliminated the effects of SFN on CSC-like properties in GC cells, and in turn enhanced the anti-cancer effects of low-dose CDDP. These findings not only suggested a mechanism whereby SFN enhanced the anti-cancer functions of CDDP, but also helped to regard SFN as a potential chemotherapeutic factor in gastric cancer.
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Xingxing
X
Wang
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Yuan
Y
Li
Department of surgery, the second affiliated hospital, Nanjing medical university, Nanjing, 211166, China.
Yi
Y
Dai
Department of surgery, the second affiliated hospital, Nanjing medical university, Nanjing, 211166, China.
Qinqiang
Q
Liu
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Shilong
S
Ning
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Jiao
J
Liu
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Zhaoxia
Z
Shen
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Dongmei
D
Zhu
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Fei
F
Jiang
Department of surgery, the second affiliated hospital, Nanjing medical university, Nanjing, 211166, China.
Jianping
J
Zhang
Key Laboratory of Modern Toxicology, Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Zhong
Z
Li
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008024:Ligands; D035683:MicroRNAs / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D034622:RNA Interference; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy; D013454:Sulfoxides
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C508603:IL6R protein, human; D017879:Isothiocyanates; D008024:Ligands; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013454:Sulfoxides; C016766:sulforaphane; D002945:Cisplatin