初探抑制一種人類結腸癌細胞的新穎化合物與其對SRC信號傳遞路徑之影響

Preliminary studies of a novel chemical compound in human colon cancer and its effect on SRC signaling pathway

陳貞伃(Chen-Yu Chen)

指導教授 ： 華國媛

國立臺北科技大學/工程學院/有機高分子研究所/碩士(2012年)

摘要

根據2011年統計，癌症是國內主要的死亡原因之一，而結腸直腸癌位居第三位。現今癌症的治療上，有手術、放射治療與抗癌藥物。但手術與放射治療的風險較高，希望可以利用抗癌藥物的專一性來抑制癌細胞的增生。SRC與mTOR在調節細胞生長、蛋白質的轉譯、代謝和信號傳遞中扮演一個重要的角色。SRC是一個致癌基因(oncogene)；mTOR是癌症藥物的標的，而SRC在mTOR的信息傳遞可能扮演調節的角色。在此研究中，我們利用雷帕霉素(Rapamycin)，mTOR inhibitor與塞卡替尼(Saracatinib)，SRC inhibitor，來瞭解實驗室先前所發現的新型抗癌化學化合物(3228)的抑制路徑。
之前我們實驗室篩選出一種化學化合物(3228)，可以抑制人類結腸直腸癌細胞株(DLD-1)的增生。我們使用不同濃度與時間，測試DLD-1細胞增生的變化；我們發現3228對DLD-1的生長產生抑制的效果。接著，我們探討3228對DLD-1中SRC與mTOR的影響為何。運用即時定量聚合酶連鎖反應法(qPCR)，相較於沒加化合物的控制組，在實驗組3228加入到DLD-1中，SRC基因的表現量是比較少的。接著利用西方墨點法來觀察SRC與mTOR的蛋白表現量與沒加3228的控制組相比較，在實驗組3228加入到DLD-1中，SRC與mTOR的表現量也是比較少的。最後，此化學化合物(3228)希望可以進一步研究開發作為一種潛在的抗癌藥物。

關鍵字

結腸直腸癌 ； SRC ； mTOR

並列摘要

According to fatality statistics in 2011, cancer is one of the leading causes of death while the incidence of colon cancer is the number third. The treatment methods of cancers include surgery, radiation therapy and chemical anti-cancer drugs. However, the surgery and radiation therapy are known with higher risks, the alternative treatment uses the specificity of the anti-cancer drugs to inhibit cancer cell proliferation. SRC and mTOR both play important roles in regulating cell growth, protein translation, metabolism and cell signaling. SRC is an oncogene, whereas mTOR is a target of anti-cancer drugs. SRC also plays a critical role in the regulation of mTOR signaling pathway. We used rapamycin, an mTOR inhibitor and saracatinib, an SRC inhibitor to elucidate a new anti-cancer chemical compound (3228) and understand the inhibition of the pathway.
First of all, our laboratory has been screened a chemical compound (3228) that showed inhibition on the survival rate of human colon cancer cells(DLD-1). We tested the cell proliferation in DLD-1 by using different concentrations and times. The result showed that 3228 has significant inhibition on the survival rate of DLD-1. Moreover, we explored the impact on SRC and mTOR in DLD-1 tested 3228. The real-time qPCR results showed that SRC gene is relatively decease in comparing compared with the control group without adding of the compound. Moreover, using western blot to measure the protein expression of SRC and mTOR, the result indicated that the SRC and mTOR protein both decreased after adding 3228. As a summary, the chemical compound (3228) can developed as an potential anti-cancer drug.

並列關鍵字

Colon cancer ； SRC ； mTOR

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