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Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune
Zhansheng Jiang1, Yanfang Yang2, Yinli Yang1
1Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Abstract:
Programmed death ligand 1 (PD-L1) as one the most important immune checkpoint was verified to involve in chemotherapy resistance in non-small cell lung cancer (NSCLC). Ginsenoside Rg3 is isolated from Chinese herb-Panax ginseng which is recognized to boost immune and has anti-cancer activity against a majority of carcinomas including NSCLC. In this study, we aim to identify whether Rg3 could attenuate the PD-L1 expression induced by resistance to cisplatin and draw out the underlying mechanisms of PD-L1 in this process. Human lung cancer cell lines A549 and A549/DDP (cisplatin-resistance) were used. Cell viability was detected by MTT assay, the PD-L1, Akt and NF-κB p65 protein expression were detected using Western blot analysis, the T cells cytotoxity to tumor cells was detected by crystal violet staining living residual tumor cells after coculture of tumor cells and T cells. The results showed that Rg3 could inhibit the growth and alleviate the resistant to cisplatin of A549/DDP cells. PD-L1 was overexpression in A549/DDP cells than A549 cells. Rg3 could decrease the PD-L1 expression induced by chemoresistance and resume the T cells cytotoxity to cancer cells. NF-κB p65 and Akt were involved in the PD-L1 overexpression and restrained by Rg3. Therefore, Rg3 could be regarded as a new agent targeting PD-L1 in chemotherapy refractory NSCLC.
Insights
Ginsenoside Rg3 combats cisplatin resistance in non-small cell lung cancer (NSCLC) by reducing PD-L1 expression. This natural compound restores T cell activity against cancer cells, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Programmed death ligand 1 (PD-L1) is a key immune checkpoint implicated in chemotherapy resistance in non-small cell lung cancer (NSCLC).
- Ginsenoside Rg3, derived from Panax ginseng, exhibits anti-cancer properties and immune-boosting effects relevant to NSCLC treatment.
Purpose of the Study:
- To investigate if Ginsenoside Rg3 can reduce PD-L1 expression in cisplatin-resistant NSCLC.
- To elucidate the underlying mechanisms by which Rg3 affects PD-L1 expression and chemoresistance.
Main Methods:
- Utilized human lung cancer cell lines (A549 and cisplatin-resistant A549/DDP).
- Assessed cell viability (MTT assay), protein expression (Western blot for PD-L1, Akt, NF-κB p65), and T cell cytotoxicity (crystal violet staining).
Main Results:
- Ginsenoside Rg3 inhibited A549/DDP cell growth and reduced cisplatin resistance.
- PD-L1 was overexpressed in resistant cells; Rg3 decreased this expression and restored T cell-mediated cytotoxicity.
- Rg3 suppressed the Akt and NF-κB p65 pathways involved in PD-L1 overexpression.
Conclusions:
- Ginsenoside Rg3 demonstrates potential as a novel therapeutic agent targeting PD-L1 in chemotherapy-refractory NSCLC.
- Rg3 may overcome chemoresistance by modulating the PD-L1 immune checkpoint via the Akt and NF-κB pathways.