| 摘要: | 結直腸癌是全球癌症死亡率的主要原因之一。儘管約70％至80％的患者適合手術切除，但有約 50％的患者會發展成轉移性疾病。這些患者需接受全身化學藥物治療。化學治療最常使用的化療藥物為 5-fluorouracil (5-FU)，但使用 5-FU 有兩個主要問題：腫瘤的抗藥性和對正常細胞的毒性。本研究的目的探討自虎杖根乙酸乙酯分離物（PcE(H)EAs），其中包括虎杖乙酸乙酯分離物（PcE(H)EA），白藜蘆醇苷，白藜蘆醇，F2a（Anthraglycoside B）和大黃素對 HT-29 細胞增殖，細胞凋亡，氧化壓力，基因毒性和 caspase-3，AP-1 和 NF-κB 表現的影響。結果顯示， PcE(H)EAs 皆能抑制 HT-29 細胞增殖。抗增殖作用的順序分別為白藜蘆醇、F2a、大黃素、PcE(H)EA 和白藜蘆醇苷。具體而言，以 F2a 誘導細胞凋亡的影響發現是依賴於隨時間而增加的基因毒性，且在 12 至 24 小時會抑制 NF-κB ，並於 24 小時活化 AP-1。大黃素可能有助於在 3 至 12 小時細胞內 ROS 表現，並在 6 小時活化 AP-1，但在 12 小時抑制 NF-κB 表現，而降低腫瘤細胞的生存。此外，聯合5-FU與白藜蘆醇苷、白藜蘆醇或 F2a 有較好的協同抑制 HT-29細胞增殖影響。總之，這些研究闡明了 F2a 和大黃素可能的分子機制和抗癌功效。然而，PcE(H)EAs 的應用及分子機制將續要更深入探討。
Colorectal cancer is one of the leading causes of cancer mortality worldwide. Although 70-80% of patients are eligible for curative surgical resection at the time of diagnosis, approximately 50% of all newly diagnosed patients ultimately develop metastatic disease. The chemistry treatment of the most commonly used chemotherapy drug 5-fluorouracil (5-FU), but the use of 5-FU has two major problems: tumor resistance and the toxicity to normal cells. The aim of this study was to analyze the effects of ethyl acetate subfractions from Polygonum cuspidatum root (PcE(H)EAs), including ethyl acetate extract from Polygonum cuspidatum root (PcE(H)EA), Piceid, Resveratrol, F2a (Anthraglycoside B) and Emodin on cell proliferation, apoptosis, oxidative stress, genotoxicity and the expressions of PARP, caspase 3, NF-κB and AP-1 in HT-29 cell lines. On the other hand, the enhancement of the 5-FU chemotherapeutic effect in combination with PcE(H)EAs on HT-29 were investigated according to Chou and Talalay method (median-effect principle). Results showed that PcE(H)EAs all could inhibit HT-29 proliferation. Anti-proliferative effect of the order is resveratrol, F2a (anthraglycoside B), emodin, PcE(H)EA and piceid. Specifically, apoptotic induction effects of F2a were found to rely on genotoxicity increased with time, and the inhibition of NF-κB at 12-24 hours and the activation of AP-1 at 24 hours. However, decreasing in cancer cell survival of emodin probably contributes to the observed intracellular ROS accumulation at 3-12 hours and the activation of AP-1 at 6 hours, but the inhibition of NF-κB at 12 hours. Besides, combined 5-FU with piceid, resveratrol or F2a had better synergism effects on inhibition of HT-29 proliferation. In conclusion, these studies elucidated the possible molecular mechanisms and therapeutic efficacy of F2a and emodin for anti-cancer. However, the applications and molecular mechanisms of PcE(H)EAs will need to continue in-depth investigation. |
