Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models
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-beta-mediated PI3K/Akt/GSK-3 beta 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-beta-mediated PI3K/Akt/GSK-3 beta/Snail signaling pathway. The clinical transformation of Plasmodium immunotherapy combined with Gem for lung cancer is worthy of expectation.
基金:
Open Project of the
State Key Laboratory Respiratory Disease (grant number: SKLRDOP-
201802), Program Grant of Guangzhou Innovation Leading
Team in Sciences and Technologies (grant number: 201909010007)
and the Applied Basic Research Projects of Yunnan Province (grant
number: 202101AY070001-084).
第一作者机构:[1]Kunming Med Univ, Affiliated Hosp 1, Dept Med Oncol, Kunming, Yunnan, Peoples R China[2]Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Ctr Infect & Immun, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[2]Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Ctr Infect & Immun, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China[3]Chinese Acad Sci, Lamvac Guangzhou Biomed Technol Co Ltd, Guangzhou, Guangdong, Peoples R China
推荐引用方式(GB/T 7714):
Chen Xiao,Tao Zhu,Liang Yun,et al.Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models[J].FRONTIERS IN ONCOLOGY.2023,13:doi:10.3389/fonc.2023.1181176.
APA:
Chen, Xiao,Tao, Zhu,Liang, Yun,Ma, Meng,Adah, Dickson...&Yang, Zhaoqing.(2023).Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models.FRONTIERS IN ONCOLOGY,13,
MLA:
Chen, Xiao,et al."Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models".FRONTIERS IN ONCOLOGY 13.(2023)