| 摘要: | 肺癌在全球所有癌症種類當中是最常見的死亡原因，據估計，在2008年即造成138萬人死於肺癌，這佔了2008年全球死於癌症的18%，相當於每五個癌症病患就有一人死於肺癌。而在肺癌所有種類當中，非小細胞肺癌(NSCLC)所佔的比例最高，佔所有種類的87%。相較於小細胞肺癌，非小細胞肺癌具有對化療藥物不敏感的特性，所以主要的治療手段會以手術切除為主，但在術前或術後常以針對患者適合的化療藥物作為治療。而很顯然地,成功的機率與肺癌的級別有很大程度的相關性，在較後期,也就是stage 3和4的患者則在手術切除後，以platinum類的化療藥物做輔助治療的手段，會利用cisplatin做單獨的給予或者是搭配其他化療用藥，輔助治療即針對較晚期肺癌在術前或術後做為新的治療方式，新型的輔助治療主要是為了使腫瘤變小使手術結果更容易更有效。利用高內涵篩選技術[68]， 針對300個小分子化合物和7個同分異構物進行兩種非小細胞肺癌的癌細胞株的細胞毒殺測試，分析出啶黃素為非小細胞肺癌的有效藥物。一方面啶黃素會造成人類非小細胞肺癌的細胞型態改變及同時地依給予濃度的增加而引發細胞程序性的死亡。另一方面， 藉由流式細胞儀的實驗得知啶黃素會導致A549肺腺癌細胞細胞阻塞在 G2/M 週期中停止生長而在動物體內試驗當中，將A549肺癌細胞以尾部靜脈注射使裸鼠帶有癌細胞，接著在第十天開始藉由腹腔注射的方式每天給予啶黃素(2毫克/公斤)並持續五週，實驗結果發現給予啶黃素處理的老鼠相較於沒有給予任何處理的老鼠明顯地具有相對較小的腫瘤大小及較少肺臟表面的腫瘤斑點；同樣地，在肺臟切片中我們也發現肺纖維化的程度顯著地降低。結論是，我們驗證了啶黃素的處理下導致老鼠體內腫瘤生長的停滯，提供了另一項針對非小細胞肺癌細胞的抗腫瘤方針。
Lung cancer is the most common cause of cancer death worldwide, estimated to be responsible for 1.38 million deaths in 2008. This equates to 18%, or around 1 in 5, of all cancer deaths in the world in 2008. Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small cell lung carcinoma (SCLC). As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy is increasingly being used both pre-operatively (neoadjuvant chemotherapy) and post-operatively (adjuvant chemotherapy). Obviously the success rate in this case, as with all stages, depends on the quality and accuracy of the lung cancer staging. The standard of care in the treatment of NSCLC is to use a platinum-based chemotherapeutic agent, especially in advanced disease (stages III and especially IV). For higher stages of lung cancer (stages III and IV) or 2) as adjuvant therapy, that is, to be used after surgery or 3) as neoadjuvant therapy, which is treatment before surgery. Neoadjuvant therapy is done to make the tumor smaller so that surgery will be easier or more effective. Using high content screening(HCS) (96 well) of the cytotoxic activity of 300 small molecule compounds from a commercial library and seven distinct structural isomers in two non-small cell lung cancer cells identified Acriflavine as a NSCLC active drug. The Lead to cell changes (morphology) and induced the process of programmed cell death simultaneously in dose-dependent manner in human NSCLC cell lines. Furthermore, Acriflavine caused cell growth arrest in G2/M phase in A549 cell line by flow cytometry analysis. In vivo testing, nude mice bearing A549 lung cancer cell line by i.v. injection. Than treatment of nude mice was started in 10th day and continued for 35 days with Acriflavine drug(2mg/kg) by daily i.p. injection. Result of the mice treated with Acriflavine group compared with the vehicle-treated control, has distinctly decrease tumor size and tumor spots in lung surface. Likewise, we also found the fibrosis levels remarkably induced in lung slice. In conclusion, we demonstrates that Acriflavine treatment of mice bearing established tumors resulted in growth arrest, providing another anti-tumour strategy by using Acriflavine to against NSCLC cell lines. |
