Inhibition of Viticis Fructus total flavonoids on self-renewal of lung cancer stem cells derived from NCI-H446 cell line / 中草药

ABSTRACT

Objective: To examine whether and how Viticis Fructus total flavonoids (VFTF) inhibit the capacity of self-renewal in lung cancer stem cells (LCSCs) derived from human small cell lung cancer NCI-H446 cell line. Methods: NCI-H446 cell line was cultured in vitro. LCSCs were obtained and amplified by Magnetically activated cell sorting system (MACS) and suspended culture with serum-free conditioned medium. The capacity of self-renewal was detected by tumor sphere-forming assay. The protein expression levels of the self-renewal associated transcription factors, Bmi1 and p-Akt, were analyzed using Western blotting. Results: VFTF significantly suppressed the capacity of self-renewal in LCSCs, in a concentration-dependent manner (P < 0.05). The expression levels of Bmi1 and p-Akt were elevated in LCSCs, compared with parental cells. VFTF effectively down-regulated the expression levels of Bmi1 and p-Akt in LCSCs. In addition, LY294002, a PI3K specific inhibitor, enhanced the inhibition of VFTF on the capacity of self-renewal in LCSCs. Conclusion: VFTF could inhibit the self-renewal capacity of LCSCs derived from NCI-H446 cell line, which is associated with down-regulation of the expression of p-Akt and self-renewal associated transcription factors Bmi1.