利用非小細胞肺癌細胞以及動物模式探討中草藥之治療潛力

Abstract

非小細胞肺癌在肺癌中具有高發生率與致死率。文獻報導有許多中草藥含抑制腫瘤生長、血管新生和轉移的能力，同時伴隨較少的副作用。我們先前從十五種臨床上常用的中藥複方中，篩檢出三種對非小細胞肺癌細胞具有抑制能力的複方，分別為三號、五號及十四號藥方。已知此三種複方會造成A549細胞週期停滯進而抑制細胞的生長。我們更進一步使用非小細胞肺癌細胞株H460以及H520為細胞模式，評估這三種複方是否對非小細胞肺癌細胞具有一致的抑制效果，並以A549細胞株於雄性裸鼠進行腫瘤異種移植動物模式，以評估藥方的抗癌效果。在細胞模式中，我們利用細胞存活率(MTT assay)檢測十四號複方對非小細胞肺癌細胞株H460以及H520的半致死率，分別為4.5% 跟3.8%。此外，我們也發現十四號複方具有抑制細胞群落形成，以及造成細胞週期停滯在G1與G2的現象。在異種移植動物模式中，我們投予三種複方後發現三號以及十四號複方可減少腫瘤的大小，以西方墨點轉漬法進一步探討複方藥物處理的結果，我們發現這兩種複方可能藉由將腫瘤內細胞停滯在G2細胞週期以及誘導細胞凋亡的發生。本實驗的結果提供細胞以及動物實驗模式的結果顯示三號以及十四號複方可能具有抗腫瘤的潛力。Non-small cell lung carcinoma (NSCLC) is lung cancer with the highest incidence and mortality rate in the world. Some Chinese herb medicines (CHM) have been reported to have potential anti-cancer activity through reducing tumor recurrence, angiogenesis, metastasis, and drug-resistance. Our previous studies have identified Formulae 3, 5, and14, showing potential anti-cancer activity in NSCLC cell lines. These formulae were found to have anti-proliferative activity through G1 and G2 arrest toward the A549 cells. We further investigated the effect of these formulae toward another two NSCLC cancer cell lines. Using MTT assay, we have determined the IC50 of Formula 14 in NSCLC H460 and H520 to be 4.5% and 3.8%, respectively. Furthermore, Formula 14 reduced the ability of colony formation, and induced G1 and G2 arrest. In addition, we characterized their therapeutic potential in vivo using mouse xenograft tumor model. We confirmed that all the 3 formula treatment had no notable toxicity for the mice though the pathological examination of mouse kidney and liver. We found that tumor size was decreased by Formulae 3 and 14. Further investigation showed that these formulae may induce G2 arrest and apoptosis to reduce the tumor size. In conclusion, we found that Formulae 3 and 14 showed potential anti-cancer activity from both the in vitro and in vivo analyses.