以小鼠為模式建立抑制肺腺癌藥物之篩選平台

Establishment of Anti-Lung Adenocarcinoma Drug Screening Platform in Mice

洪紹文(Shao-Wen Hung) ； 陳嘉琪(Chia-Chi Chen) ； 邱健昭(Chien-Chao Chiu) ； 林壬威(Jen-Wei Lin) ； 楊程堯(Cheng-Yao Yang)

《宜蘭大學生物資源學刊》 14卷 (2018/12) Pp. 41-66

https://doi.org/10.6175/job.201812_14.0004

摘要

肺癌是全球癌症病人死亡的主要原因，本研究目的在於以A549人類肺癌細胞株誘導建立異位異種移植的A549肺癌小鼠模式，並搭配肺部組織病理學與細胞學判讀檢測技術，來建立一套抗肺癌藥物篩選平台，利用此平台來進行抗肺癌研發藥物標的篩選與治療策略設計。實驗方法利用人類肺癌A549細胞株接種於免疫缺陷老鼠（NOD SCID mice）皮下，並投予臨床抗癌藥物（5-FU或Cisplatin），後續針對腫瘤進行病變分析。由結果得知，已成功建立異位異種移植（ectopic xenotransplation）人類肺癌A549於小鼠的癌症模式與5-FU（17.5-20 mg/kg body weight, intravenous injection, thrice/week for 4 weeks）或Cisplatin（4 mg/kg body weight, intraperitoneal injection, 3 times）於癌化小鼠的治療策略。此外，搭配肺部組織病理學與細胞學判讀檢測技術的病變分析（器官轉移、細胞有絲分裂、PCNA、Pan CK與Factor-8），已成功建立一套符合生技醫藥研發抗肺癌藥物篩選平台，期望此平台未來將可運用於抗肺癌藥物篩選與治療策略設計，協助生技醫藥業者篩選有效研發標的與測試其研發藥品功效，加速進入臨床試驗。

關鍵字

異位 ； 體內 ； 肺癌 ； 平台 ； 異種移植

並列摘要

Lung cancer is the leading cause of cancer death worldwide. The purpose of this study was to establish an ectopic xenotransplantation model of human lung cancer cell line A549 in mice, and to combine with the histopathology of lung and cytological detection for the establishment of an anti-lung cancer drug screening platform. Experimental methods included that human lung cancer A549 cell line was inoculated into the subcutaneous tissue of immunodeficient mice (NOD SCID mice) and administered with clinical anti-cancer drugs (5-FU or Cisplatin), followed by lesion analysis of the tumor. According to the results, we have successfully established an ectopic xenotransplation of human lung cancer A549 in mice and the treatment strategies of 5-FU (17.5-20 mg/kg body weight, intravenous injection, thrice/week for 4 weeks) or Cisplatin (4 mg/kg body weight, intraperitoneal injection, 3 times) in tumor-bearing mice. In addition, the lesion analysis (organ metastasis, cell mitosis, PCNA, Pan CK, and Factor-8) was performed together with lung histopathological and cytometric detection techniques. In this study, a screening platform for biomedical research and development of anti-lung cancer drugs has been successfully established. We hope that the ectopic xenograft lung cancer model with therapeutic strategies with chemotherapeutic drugs will applied to the new anti-cancer drug research and development in the future.

並列關鍵字

ectopic ； In vivo ； lung cancer ； platform ； xenograft