Juan Du1, Brian Chi Yan Cheng1, Xiu-Qiong Fu1, Tao Su1, Ting Li1, Hui Guo1, Su-Mei Li1, Jin-Feng Wu1, Hua Yu1, Wen-Hua Huang2, Hui Cao3, Zhi-Ling Yu4. 1. Consun Chinese Medicines Research Centre for Renal Diseases, Hong Kong Baptist University, Hong Kong; Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong. 2. Livzon Pharmaceutical Group Co. Ltd, People Republic of China. 3. College of Pharmacy, Jinan University, Guangzhou, People Republic of China. Electronic address: kovhuicao@aliyun.com. 4. Consun Chinese Medicines Research Centre for Renal Diseases, Hong Kong Baptist University, Hong Kong; Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong. Electronic address: zlyu@hkbu.edu.hk.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: A modern agent Shenqi Fuzheng Injection (SFI), prepared from Codonopsis Radix and Astragali Radix, has been commonly used as a supplementary therapy for cancers including melanoma. This agent was derived from a formula documented in the "National Collection of Chinese Medicine Prescriptions". The formula has long been used as a remedy for Qi deficiency that is closely associated with cancer-related fatigue and poor quality of life. However, the antimelanoma mechanisms of SFI remain unclear. Here we tested if SFI exerted antimelanoma effects by reprograming the tumour immune microenvironment using in vitro assays. MATERIALS AND METHODS: The cytotoxic activities of Jurkat T cells when co-cultured with A375 cells were determined in the presence or absence of SFI. The migratory activities of Jurkat T cells were examined in the transwell assay system. The mRNA expression and production of cytokines (IL-10, TGF β and VEGF) in A375 cells in the presence or absence of SFI were determined by real-time PCR and ELISA, respectively. RESULTS: When A375 cells were co-cultured with Jurkat T cells in the presence of SFI (220µg/mL), a potent cytotoxicity effect against A375 cells was observed. Supernatants from A375 cells that were treated with SFI (110 and 220µg/mL) significantly increased the migratory capacity of Jurkat T cells in transwell assays. SFI also markedly reduced the mRNA expression levels and the release of immunosuppressive cytokines IL-10, TGF-β and VEGF in A375 cells in a concentration-dependent manner. CONCLUSIONS: SFI enhanced the cytotoxic and migratory activities of Jurkat T cells towards A375 melanoma cells. The effects were associated with SFI's suppression on immunosuppressive cytokines for their release from and gene expressions in A375 melanoma cells. These in vitro findings suggested that SFI might reprogramme the immunosuppressive melanoma microenvironment in vivo to enhance the cytotoxicity of tumour-infiltrating immune cells. This study provides a pharmacological basis for the adjunctive use of SFI in melanoma treatment.
ETHNOPHARMACOLOGICAL RELEVANCE: A modern agent Shenqi Fuzheng Injection (SFI), prepared from Codonopsis Radix and Astragali Radix, has been commonly used as a supplementary therapy for cancers including melanoma. This agent was derived from a formula documented in the "National Collection of Chinese Medicine Prescriptions". The formula has long been used as a remedy for Qi deficiency that is closely associated with cancer-related fatigue and poor quality of life. However, the antimelanoma mechanisms of SFI remain unclear. Here we tested if SFI exerted antimelanoma effects by reprograming the tumour immune microenvironment using in vitro assays. MATERIALS AND METHODS: The cytotoxic activities of Jurkat T cells when co-cultured with A375 cells were determined in the presence or absence of SFI. The migratory activities of Jurkat T cells were examined in the transwell assay system. The mRNA expression and production of cytokines (IL-10, TGF β and VEGF) in A375 cells in the presence or absence of SFI were determined by real-time PCR and ELISA, respectively. RESULTS: When A375 cells were co-cultured with Jurkat T cells in the presence of SFI (220µg/mL), a potent cytotoxicity effect against A375 cells was observed. Supernatants from A375 cells that were treated with SFI (110 and 220µg/mL) significantly increased the migratory capacity of Jurkat T cells in transwell assays. SFI also markedly reduced the mRNA expression levels and the release of immunosuppressive cytokines IL-10, TGF-β and VEGF in A375 cells in a concentration-dependent manner. CONCLUSIONS: SFI enhanced the cytotoxic and migratory activities of Jurkat T cells towards A375 melanoma cells. The effects were associated with SFI's suppression on immunosuppressive cytokines for their release from and gene expressions in A375 melanoma cells. These in vitro findings suggested that SFI might reprogramme the immunosuppressive melanoma microenvironment in vivo to enhance the cytotoxicity of tumour-infiltrating immune cells. This study provides a pharmacological basis for the adjunctive use of SFI in melanoma treatment.
Authors: Dongmei Wei; Lin Wang; Yuhan Chen; Gang Yin; Mei Jiang; Rui Liu; Hong Chen; Xiyuan Sun Journal: J Cancer Date: 2018-04-12 Impact factor: 4.207