| Abstract: | 全世界死亡原因之一是癌症所導致，其中以結腸癌致死的例子，位居癌症死亡的第三名。目前可以得知癌症會在能量產生會有異常的狀況，主要是透過有氧糖解作用，吸收大量的葡萄糖，但只產生少量的ATP，碳酸酐酶第八型(CA8)是一個新穎的蛋白，可能在能量代謝中扮演重要的角色，我們先前的研究結果顯示CA8和FAK/ Akt的路徑關係，在人類HOS骨肉瘤細胞，當降低內生性CA8表達，在葡萄糖缺乏情況下比起親代的HOS細胞，使細胞存活提高， 顯示CA8表達和能量代謝的關係。在我的研究中，我想調查CA8是否參與在調節葡萄糖代謝機制，我利用了人類SW480和SW620結腸癌細胞，以shRNA降低CA8表達，來進行研究AMPK/Beclin-1/ LC-3B 和AMPK/PARP 路徑。根據目前我的數據顯示，第一， CA8的表達在SW620細胞下降會降低細胞生長及爬行，但卻不會影響SW480細胞。第二，在SW480中卻只會增加p53及Beclin-1/LC-3B的表達，這可以顯示CA8的表達對原位癌細胞會影響自噬作用。然而，在SW620中降低CA8會增加p53及Beclin-1的表達，但卻不會對LC-3B的表達有影響。這一些結果支持轉移型大腸癌細胞比起原位大腸癌細胞，在降低CA8的反應有所不同，這可能跟在癌症藥物治療下的癌症相關。總結，CA8在大腸癌細胞中可能影響在葡萄糖代謝和細胞存活和相關分子。因此，CA8可能在未來可做為一個藥物處理的目標分子。
Cancer is a leading cause of death worldwide. Of all types of cancer, colon cancer causes the fourth-most deaths. It is known that aerobic glycolysis is the primary energy generating process in cancer development, during which little ATP is produced per unit of glucose absorbed. Carbonic anhydrase VIII (CA8) is a novel protein which may play an important role in the energy metabolism of cancer cells. Our previous results suggest that there is a significant effect of CA8 on the FAK/Akt pathway. In human osteosarcoma (HOS) cells, we showed that the knockdown of endogenous CA8 experienced higher cell survival rates in glucose-free environments, compared with parental HOS cells. Our previous data also indicated a relationship between CA8 expression and energy metabolism. In this study, I investigated whether CA8 is involved in regulating glucose metabolism. I suppressed CA8 expression through shRNA knockdown in two human colon cancer cell lines, SW480 and SW620. These cell lines were used to study, under different concentrations of glucose, whether CA8 affects AMPK/beclin-1/LC-3B and AMPK/PARP pathways. According to my results, I found that first, downregulation of CA8 can decrease cell growth and cell migration in SW620, but that can not be affected in SW480. Second, CA8 knockdown in SW480 increased p53 and Beclin-1/ LC-3B expression, indicating that expression of CA8 may influence autophagy on primary tumor cells. However, CA8 knockdown in SW620 increased beclin-1 and p53 expression, but has no effect on the level of LC-3B expression. These results suggest that metastatic colon cancer cells respond differently to CA8 knockdown, compared with primary colon cancer cells, which may be relevant to the cell survival rate under cancer drug treatment. In summary, CA8 may affect glucose metabolism- and cell survival-related molecules in colon cancer. Therefore, CA8 can potentially be an effective target in cancer therapy. |
