Que Zu-Jun, Yao Jia-Liang, Zhou Zhi-Yi, Yu Pan, Luo Bin, Li He-Gen, Liu Jia-Xiang, Xu Hong-Xi, Tian Jian-Hui
Institute of Traditional Chinese Medicine Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China.
Institute of Traditional Chinese Medicine Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, China.
J Ethnopharmacol. 2021 Jul 15;275:114175. doi: 10.1016/j.jep.2021.114175. Epub 2021 Apr 30.
Circulating tumor cells (CTCs) play an important role in tumor metastasis and may be a target for metastasis prevention. The traditional Chinese medicine Jinfukang functions to improve immunity, prevent metastasis, and prolong lung cancer patient survival periods. Yet, whether Jinfukang prevents metastasis by regulating immune cells to clearance CTCs is still unknown.
To explore the anti-metastasis mechanism of Jinfukang from the perspective of regulating NK cells to clear CTCs.
CTC-TJH-01 cell was treated with Jinfukang. Cytokine chip was used to detect cytokines in cell culture supernatant. Lymphocyte recruitment assay was detected by Transwell and flow cytometry. Protein expression was analysis by Western blot. LDH kit was used to detect cytotoxicity. NOD-SCID mice used for tail vein injection to study lung metastasis.
Jinfukang could promote the expression and secretion of the chemokine CX3CL1 by CTCs. In addition, Jinfukang could promote the recruitment of natural killer (NK) cells by CTCs and significantly increase the cytotoxic effect of NK cells on CTCs. Moreover, Jinfukang could upregulate the expression of FasL and promote the secretion of TNF-α by NK cells and that NK cells could induce the apoptosis of CTCs through the Fas/FasL signaling pathway. Finally, we confirmed that Jinfukang could promote NK cells to kill CTCs and then inhibit lung cancer metastasis in vivo. The above effects of Jinfukang could be partially reversed by an anti-CX3CL1 mAb.
These results suggest that Jinfukang may prevent lung cancer metastasis by enhancing the clearance of CTCs in the peripheral blood by NK cells, providing evidence for the anti-metastasis effect of Jinfukang.
循环肿瘤细胞（CTC）在肿瘤转移中起重要作用，可能是预防转移的靶点。中药金复康具有提高免疫力、预防转移和延长肺癌患者生存期的作用。然而，金复康是否通过调节免疫细胞清除CTC来预防转移尚不清楚。
从调节自然杀伤细胞（NK）清除CTC的角度探讨金复康的抗转移机制。
用金复康处理CTC-TJH-01细胞。采用细胞因子芯片检测细胞培养上清中的细胞因子。通过Transwell和流式细胞术检测淋巴细胞募集情况。用蛋白质印迹法分析蛋白质表达。用乳酸脱氢酶试剂盒检测细胞毒性。将NOD-SCID小鼠用于尾静脉注射以研究肺转移。
金复康可促进CTC表达和分泌趋化因子CX3CL1。此外，金复康可促进CTC募集自然杀伤（NK）细胞，并显著增强NK细胞对CTC的细胞毒性作用。而且，金复康可上调FasL的表达并促进NK细胞分泌TNF-α，NK细胞可通过Fas/FasL信号通路诱导CTC凋亡。最后，我们证实金复康可促进NK细胞杀伤CTC，进而在体内抑制肺癌转移。金复康的上述作用可被抗CX3CL1单克隆抗体部分逆转。
这些结果表明，金复康可能通过增强NK细胞对外周血中CTC的清除来预防肺癌转移，为金复康的抗转移作用提供了证据。
