Abstract: AIM: To investigate the sensitization of flavonoids from Tetrastigma hemsleyanum (FTH) on gefitinib (GEF)-resistant lung adenocarcinoma cells.  METHODS: The viabilities of A549 and A549/GR cells treated with FTH and GEF were detected by MTT method. The apoptotic rates and cell cycles of A549/GR cells treated with FTH and GEF were detected by Flow cytometry. The anti-tumor effects of flavonoids from FTH and GEF were assayed in A549/GR tumor-bearing mice. The expressions of proteins (PTEN, PI3K, p-PI3K, AKT, p-AKT) were detected by Western blot analysis. RESULTS: Compared with GEF group, FTH significantly enhanced the inhibition of GEF on the proliferation of A549/GR cells (P<0.05). Combination with FTH and GEF significantly increased the apoptosis of A549/GR cells which were arrested at the G0/G1 stage (P<0.05). The in vivo results showed that combination with FTH and GEF significantly inhibited the tumor growth of A549/GR in mice (P<0.05). Furthermore, this combination significantly downregulated the expressions of p-PI3K and p-AKT (P<0.05), but upregulated the expressions of PTEN (P<0.05). CONCLUSION: FTH increases the sensitivity to gefitinib by modulating PTEN/PI3K/AKT pathway in acquired GEF resistance of non-small cell lung cancer.

Key words: Tetrastigma hemsleyanum Radix, flavonoids, EGFR-TKIs, resistance, PTEN/PI3K/AKT