|Enhancement of gefitinib-induced growth inhibition by Marsdenia tenacissima extract in non-small cell lung cancer cells expressing wild or mutant EGFR|
|Han, Shu-Yan1; Ding, Hui-Rong2; Zhao, Wei3; Teng, Fei1; Li, Ping-Ping1|
|关键词||Marsdenia Tenacissima Extract (Mte) Gefitinib Non-small Cell Lung Cancer (Nsclc) Combination Egfr Related Pathway|
|刊名||BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE|
|WOS标题词||Science & Technology|
|类目[WOS]||Integrative & Complementary Medicine|
|研究领域[WOS]||Integrative & Complementary Medicine|
|关键词[WOS]||FACTOR RECEPTOR ; C-MET ; MUTATIONS ; LINES ; SENSITIVITY ; COMBINATION ; ERLOTINIB ; SURVIVAL ; KINASES ; PATHWAY|
Background: Non-small cell lung cancer (NSCLC) expressed high levels of epidermal growth factor receptor (EGFR). Gefitinib (Iressa) has demonstrated clinical efficacy in NSCLC patients harboring EGFR mutations or refractory to chemotherapy. However, most of NSCLC patients are with wild type EGFR, and showed limited response to gefitinib. Therefore, to develop new effective therapeutic interventions for NSCLC is still required. Our previous study showed Marsdenia tenacissima extract (MTE) restored gefitinib efficacy in the resistant NSCLC cells, but whether MTE acts in the gefitinib-sensitive NSCLC cells is the same as it in the resistant one is unknown.
Methods: Dose response curves for gefitinib and MTE were generated for two sensitive NSCLC cell lines with mutant or wild type EGFR status. Three different sequential combinations of MTE and gefitinib on cell growth were evaluated using IC50 and Combination Index approaches. The flow cytometric method was used to detect cell apoptosis and cell cycle profile. The impact of MTE combined with gefitinib on cell molecular network response was studied by Western blotting.
Results: Unlike in the resistant NSCLC cells, our results revealed that low cytotoxic dose of MTE (8 mg/ml) combined gefitinib with three different schedules synergistically or additively enhanced the growth inhibition of gefitinib. Among which, MTE -> MTE + gefitinib treatment was the most effective one. MTE markedly prompted cell cycle arrest and apoptosis caused by gefitinib both in EGFR mutant (HCC827) and wild type of NSCLC cells (H292). The Western blotting results showed that MTE -> MTE + gefitinib treatment further enhanced the suppression of gefitinib on cell growth and apoptosis pathway such as ERK1/2 and PI3K/Akt/mTOR. This combination also blocked the activation of EGFR and c-Met which have cross-talk with each other. Unlike in gefitinib-resistant NSCLC cells, MTE alone also demonstrated certain unexpected modulation on EGFR related cell signal pathways in the sensitive cells.
Conclusion: Our results suggest that MTE is a promising herbal medicine to improve gefitinib efficacy in NSCLC regardless of EGFR status. However, why MTE acted differently between gefitinib-sensitive and -resistant NSCLC cells needs a further research.
|项目编号||7112027 ; 20090450009 ; JJ2010-17|
|资助机构||Beijing Municipal Natural Science Foundation ; China Postdoctoral Science Foundation ; Beijing Municipal Traditional Chinese Medicine Technology Foundation|
|作者单位||1.Cent Lab Biochem & Mol Biol, Haidian Dist, Peoples R China|
2.Peking Univ, Canc Hosp & Inst, Dept Integrat Chinese & Western Med, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China
3.Peking Univ, Canc Hosp & Inst, Dept Cell Biol, Beijing 100142, Peoples R China
|Han, Shu-Yan,Ding, Hui-Rong,Zhao, Wei,et al. Enhancement of gefitinib-induced growth inhibition by Marsdenia tenacissima extract in non-small cell lung cancer cells expressing wild or mutant EGFR[J]. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE,2014,14.|
|APA||Han, Shu-Yan,Ding, Hui-Rong,Zhao, Wei,Teng, Fei,&Li, Ping-Ping.(2014).Enhancement of gefitinib-induced growth inhibition by Marsdenia tenacissima extract in non-small cell lung cancer cells expressing wild or mutant EGFR.BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE,14.|
|MLA||Han, Shu-Yan,et al."Enhancement of gefitinib-induced growth inhibition by Marsdenia tenacissima extract in non-small cell lung cancer cells expressing wild or mutant EGFR".BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 14(2014).|