Stephania Tetrandra and Ginseng-Containing Chinese Herbal Formulation NSENL Reverses Cisplatin Resistance in Lung Cancer Xenografts

Abstract

Chinese Herbal Formulation, supplement energy and nourish lung (SENL), effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multi-drug resistance (MDR) in lung cancer cells in vitro. The present study is designed to assess the effect of a New SENL (NSENL, modification of SENL) formulation on resistance to chemotherapy of cisplatin (DDP)-resistant human lung cancer cell line (A549/DDP) xenografts in nude mice. We assessed six constituents in NSENL by high performance liquid chromatography (HPLC). BALB/c nude mice harboring A549/DDP cell xenografts were established to assess the antitumor effect of NSENL and its impact on the expression of MDR related genes. The six constituents in NSENL, including ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rg3, astragaloside IV, ophiopogonin D and tetrandrine were quantitated simultaneously by HPLC. The combination of NSENL with DDP significantly inhibited tumor growth at a rate of up to 66.8% ([Formula: see text]). In addition, NSENL as monotherapy or combined with DDP downregulated multidrug resistance-associated protein 1 (MRP1), basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) at both the mRNA and protein levels ([Formula: see text]), reduced glutathione S-transferase π (GST-π) protein expression and tumor microvascular density as well as decreased phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) ([Formula: see text]). These findings demonstrated that NSENL can reverse MDR in A549/DDP cells in vivo, an effect possibly associated with downregulation of MDR-associated genes as well as inhibition of bFGF/FGFR and phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathways.