Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models
ObjectiveOur 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 immuno...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1181176/full |
| _version_ | 1797658121426960384 |
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| author | Xiao Chen Xiao Chen Zhu Tao Zhu Tao Yun Liang Yun Liang Meng Ma Meng Ma Dickson Adah Wenting Ding Lili Chen Xiaofen Li Linglin Dai Songwe Fanuel Songwe Fanuel Siting Zhao Siting Zhao Wen Hu Donghai Wu Ziyuan Duan Fang Zhou Li Qin Xiaoping Chen Xiaoping Chen Zhaoqing Yang |
| author_facet | Xiao Chen Xiao Chen Zhu Tao Zhu Tao Yun Liang Yun Liang Meng Ma Meng Ma Dickson Adah Wenting Ding Lili Chen Xiaofen Li Linglin Dai Songwe Fanuel Songwe Fanuel Siting Zhao Siting Zhao Wen Hu Donghai Wu Ziyuan Duan Fang Zhou Li Qin Xiaoping Chen Xiaoping Chen Zhaoqing Yang |
| author_sort | Xiao Chen |
| collection | DOAJ |
| description | ObjectiveOur 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.MethodsWe 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.ResultsWe 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.ConclusionThe 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. |
| first_indexed | 2024-03-11T17:54:28Z |
| format | Article |
| id | doaj.art-c73844bff449455f9414c651a204942e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-11T17:54:28Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-c73844bff449455f9414c651a204942e2023-10-17T20:26:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-10-011310.3389/fonc.2023.11811761181176Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer modelsXiao Chen0Xiao Chen1Zhu Tao2Zhu Tao3Yun Liang4Yun Liang5Meng Ma6Meng Ma7Dickson Adah8Wenting Ding9Lili Chen10Xiaofen Li11Linglin Dai12Songwe Fanuel13Songwe Fanuel14Siting Zhao15Siting Zhao16Wen Hu17Donghai Wu18Ziyuan Duan19Fang Zhou20Li Qin21Xiaoping Chen22Xiaoping Chen23Zhaoqing Yang24Department of Medical Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaCAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaThe Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaCAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaDepartment of Applied Biosciences and Biotechnology, Faculty of Science and Technology, Midlands State University, Gweru, ZimbabweState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaCAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, ChinaCAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaCAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, ChinaCAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, Guangdong, ChinaCAS-Lamvac (Guangzhou) Biomedical Technology Co., Ltd., Guangzhou, Guangdong, ChinaDepartment of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan, ChinaObjectiveOur 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.MethodsWe 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.ResultsWe 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.1181176/fullPlasmodium immunotherapyPlasmodium chabaudi ASSgemcitabineanticancer effectsynergismmouse lung cancer model |
| spellingShingle | Xiao Chen Xiao Chen Zhu Tao Zhu Tao Yun Liang Yun Liang Meng Ma Meng Ma Dickson Adah Wenting Ding Lili Chen Xiaofen Li Linglin Dai Songwe Fanuel Songwe Fanuel Siting Zhao Siting Zhao Wen Hu Donghai Wu Ziyuan Duan Fang Zhou Li Qin Xiaoping Chen Xiaoping Chen Zhaoqing Yang Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models Frontiers in Oncology Plasmodium immunotherapy Plasmodium chabaudi ASS gemcitabine anticancer effect synergism mouse lung cancer model |
| title | Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models |
| title_full | Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models |
| title_fullStr | Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models |
| title_full_unstemmed | Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models |
| title_short | Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models |
| title_sort | plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine lewis lung cancer models |
| topic | Plasmodium immunotherapy Plasmodium chabaudi ASS gemcitabine anticancer effect synergism mouse lung cancer model |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1181176/full |
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