Meng-Jun Qiu1, Xiao-Xiao He1, Ning-Rui Bi2, Meng-Meng Wang1, Zhi-Fan Xiong3, Sheng-Li Yang4. 1. Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China. 2. Department of HepatobiliarySurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, China. 3. Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China. Electronic address: xiongzhifan@126.com. 4. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: yangshengli2014@yahoo.com.
Abstract
BACKGROUND: The molecular mechanisms involved in the development and metastasis of hepatocellular carcinoma (HCC) are complex. Molecule-targeted drugs are characterized by strong specificity and low toxicity, but the clinical research of these drugs still exhibits many difficulties, such as poor target specificity. With the in-depth study of the tumor immunological theory, therapies based on overcoming the tumor immune escape to produce a specific effective tumor immune response has gradually become a hot topic in tumor research. We hope that by studying the effects of liver-targeted drugs on the expression of immune-related proteins in hepatocellular carcinoma cells, we will find a potential link to further guide the clinical drug use. METHODS: Human hepatoma Hep3B cells were used to establish liver cancer xenografts by inoculating 40 BALB/c nude mice. The following five groups of mice (8 mice per group) were randomly set up: lenvatinib group, apatinib group, sorafenib group, regorafenib group, and dimethyl sulfoxide (DMSO) group. After treatment, we analyzed PD-L1 and B7-H3 mRNA using the real-time polymerase chain reaction (PCR) assay and assessed the PD-L1 and B7-H3 protein expression by Western immunoblotting. RESULTS: Real-time PCR results suggested that the mRNA expression of PD-L1 in the lenvatinib group was significantly higher than that in the control group, while its expression in the regorafenib group was significantly lower than that in the control group (both p < .05). Western immunoblotting results suggested that, compared with the control group, PD-L1 protein was increased in the lenvatinib group, while its expression in the regorafenib group was decreased. CONCLUSION: Lenvatinib and regorafenib affected the expression of PD-L1 in the process of anti-HCC.
BACKGROUND: The molecular mechanisms involved in the development and metastasis of hepatocellular carcinoma (HCC) are complex. Molecule-targeted drugs are characterized by strong specificity and low toxicity, but the clinical research of these drugs still exhibits many difficulties, such as poor target specificity. With the in-depth study of the tumor immunological theory, therapies based on overcoming the tumor immune escape to produce a specific effective tumor immune response has gradually become a hot topic in tumor research. We hope that by studying the effects of liver-targeted drugs on the expression of immune-related proteins in hepatocellular carcinoma cells, we will find a potential link to further guide the clinical drug use. METHODS:Humanhepatoma Hep3B cells were used to establish liver cancer xenografts by inoculating 40 BALB/c nude mice. The following five groups of mice (8 mice per group) were randomly set up: lenvatinib group, apatinib group, sorafenib group, regorafenib group, and dimethyl sulfoxide (DMSO) group. After treatment, we analyzed PD-L1 and B7-H3 mRNA using the real-time polymerase chain reaction (PCR) assay and assessed the PD-L1 and B7-H3 protein expression by Western immunoblotting. RESULTS: Real-time PCR results suggested that the mRNA expression of PD-L1 in the lenvatinib group was significantly higher than that in the control group, while its expression in the regorafenib group was significantly lower than that in the control group (both p < .05). Western immunoblotting results suggested that, compared with the control group, PD-L1 protein was increased in the lenvatinib group, while its expression in the regorafenib group was decreased. CONCLUSION:Lenvatinib and regorafenib affected the expression of PD-L1 in the process of anti-HCC.
Authors: Flavia Fondevila; Carolina Méndez-Blanco; Paula Fernández-Palanca; Javier González-Gallego; José L Mauriz Journal: Exp Mol Med Date: 2019-09-24 Impact factor: 8.718