Please use this identifier to cite or link to this item: https://cris.library.msu.ac.zw//handle/11408/6010
Title: Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models
Authors: Xiao Chen
Zhu Tao
Yun Liang
Meng Ma
Dickson Adah
Wenting Ding
Lili Chen
Xiaofen Li
Linglin Dai
Songwe Fanuel
Siting Zhao
Wen Hu
Donghai Wu
Ziyuan Duan
Fang Zhou
Li Qin
Xiaoping Chen
Zhaoqing Yang
Qun Xue
Department of Medical Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China; CAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, China,
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China; The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China
CAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China; Department of Applied Biosciences and Biotechnology, Faculty of Science and Technology, Midlands State University, Gweru, Zimbabwe
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China; CAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, China
CAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China
CAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, China
CAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, China
State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, China; CAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, China
Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan, China
Hospital of Nantong University, China
Keywords: Plasmodium immunotherapy
Plasmodium chabaudi ASS
gemcitabine
anticancer effect
synergism
mouse lung cancer model
Issue Date: 17-Oct-2023
Publisher: Frontiers Media
Abstract: Objective: Our previous studies have demonstrated that Plasmodium immunotherapy (infection) has antitumor effects in mice. However, as a new form of immunotherapy, this therapy has a weakness: its specific killing effect on tumor cells is relatively weak. Therefore, we tested whether Plasmodium immunotherapy combined with gemcitabine (Gem), a representative chemotherapy drug, has synergistic antitumor effects. Methods: We designed subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) models to test the antitumor effect of Plasmodium chabaudi ASS (Pc) infection in combination with Gem treatment and explored its underlying mechanisms. Results: We found that both Pc infection alone and Gem treatment alone significantly inhibited tumor growth in the subcutaneous model, and combination therapy was more effective than either monotherapy. Monotherapy only tended to prolong the survival of tumor-bearing mice, while the combination therapy significantly extended the survival of mice, indicating a significant synergistic effect of the combination. In the mechanistic experiments, we found that the combination therapy significantly upregulated E-cadherin and downregulated Snail protein expression levels, thus inhibiting epithelial-mesenchymal transition (EMT) of tumor cells, which may be due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β signaling pathway. Conclusion: The combination of Pc and Gem plays a synergistic role in inhibiting tumor growth and metastasis, and prolonging mice survival in murine lung cancer models. These effects are partially attributed to the inhibition of EMT of tumor cells, which is potentially due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β/Snail signaling pathway. The clinical transformation of Plasmodium immunotherapy combined with Gem for lung cancer is worthy of expectation.
URI: https://cris.library.msu.ac.zw//handle/11408/6010
Appears in Collections:Research Papers

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