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Osimertinib, as a first-line therapeutic agent for non-small cell lung cancer (NSCLC), significantly prolongs patients' progression-free survival and overall survival. However, the development of acquired resistance to this agent remains an unavoidable clinical challenge. This study investigated platycodin D (PD) as a potential resistance modulator. Cell viability was assessed using the CCK-8 assay; cell proliferation was detected using the colony formation assay; cytotoxic effects were evaluated via lactate dehydrogenase (LDH) release; apoptosis was detected by PI/Hoechst double staining and flow cytometry; and the expression of apoptosis-related proteins and key components of the Akt/p70S6K pathway as well as phosphorylation levels were examined by Western blot. Results demonstrated that platycodin D suppressed the viability of osimertinib-acquired resistant NSCLC cells and exhibited synergistic antiproliferative effects when combined with osimertinib. The combination treatment significantly inhibited cell growth and induced apoptosis, with effects markedly stronger than either agent alone. Mechanistic studies revealed that the combined treatment more effectively suppressed the phosphorylation of Akt and p70S6K as compared to the single treatment group. In conclusion, this study reveals that platycodin D can enhance the cytotoxic effect of osimertinib against resistant NSCLC cells and reverse osimertinib resistance by inhibiting the Akt/p70S6K signaling pathway, thereby providing a promising strategy to overcome osimertinib resistance.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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