2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38796Radiotherapy and chemotherapy are the major therapeutic treatments when the tumor can not be surgically removed. Studies showed that radiation causes genetic changes of cancer cells that lead to radioresistance. Metastasis is also resulted because of the increased secretion of VEGF and induced activity of MMPs by radiation exposure. Although chemotherapy is the most common applied treatment, it causes serious physiological side effects, and patients usually develop resistance to the used anticancer drugs that, in turn, fails the therapy. Multidrug resistance (MDR) is responsible for more than 50% of cancer drug resistance with a multifactorial mechanism. In order to solve the resistance of cancer therapy, recent research is focused on the application of food or supplement as adjuvant of conventional treatment to ease side effects or to enhance cytotoxicity of radiation and cancer drug. That is using sensitizer to improve the sensitivity of cancer cells toward therapy hoping for better response and preventing metastasis. Mulberry is rich in anthocyanin, flavonoides (quercetin, gossypetin, hibiscetin) and protocatechuic acid which are proved to possess the abilities for antioxidation, chemoprevention and preventing cardiovascular diseases. In this sub-project, both cell and animal models will be used to demonstrate the enhancing effect of mulberry extracts on the cytotoxicity of chemo- and radiotherapy for different human cancerous cells, in order to evaluate the possibility of developing mulberry extracts as healthy food supplement for cancer therapy. In the first year, different cancerous cell lines will be treated with non-toxic doses of mulberry extracts (water extract, polyphenols and anthocyanins) in combined with radiation or anticancer drug to observe the enhancing effects of mulberry and to look into the possible mechanism of cell death. The long-term and short-tern toxicity, the type of cell death, and the expression and activation of signal transduction pathway members will be analyzed. In the second year, the findings of cell studies will be conducted in an animal model (tumor xenograft in null mice) to confirm the in vivo function of mulberry extracts as sensitizers of chemo- and radio-therapy. The tumorous angiogenesis and inflammatory response will also be investigated beside molecular mechanisms. In the third year, both cell and animal studies will be conducted to evaluate the inhibitory effect of mulberry extracts on the migration and metastatic ability of cancer cells. Boyden camber and zymograph techniques will be used to analyze the migration and invasion activities of cancer cells after exposed to radiation or anticancer drug with the supplement of mulberry extracts. For in vivo effect, nude mice will receive cancer cells via tail vein, and metastasis to distant organs will be observed after combined treatments of chemo- or radio-therapy with mulberry extracts.癌症的治療早期發現時以手術切除為主，對於無法手術切除的腫 瘤，治療的方式則以化學治療及放射線治療為主。文獻指出當細胞接 受放射線刺激後會引發某些基因的表現，使癌細胞產生放射線抵抗性 (radioresistant)，而且放射線會刺激血管生長因子VEGF 以及一些蛋 白質分解酵素MMPs 的表現，促使癌細胞的侵入及轉移的能力增加 而造成遠端器官的轉移。化學治療雖是癌症治療的主要策略，然而其 過程中除了容易產生許多生理上的副作用之外，多數病人對於現今臨 床使用的抗癌藥多會產生抗藥性，導致治療失敗。百分之五十以上的 癌症其抗藥性是導因於多重抗藥性(Multidrug resistance, MDR)，其機 轉是多因素所造成的。為了解決癌症治療抗性的問題，目前正積極研 究於治療過程中給予某些食品或藥品添加物，以減緩病人的不適，或 降低治療的劑量，或是增強其殺傷力，來提高治癒的機會。亦即使用 增敏劑(sensitizer)來增加腫瘤對治療的敏感性，加強療效，免於復發 與轉移的發生。 桑椹(mulberry)具有豐富的色素成分，而許多的色素成分被證實是 一種很好的抗氧化物質。此外桑椹亦含有豐富的flavonoides（如 quercetin，gossypetin，hibiscetin）與原兒茶酸（protocatechuic acid）， 這些成份都具有抗氧化、防癌、抑制心血管病變，極具發展的價值。 本子計劃中將以細胞與動物模式探討桑椹萃取物合併放射線治療與 化學治療對毒殺多種人類癌細胞是否有加強之成效，以評估桑椹萃取 物是否可作為化放療的增敏劑，發展為輔助癌症治療的保健食品。 第一年: 以細胞實驗分別評估無毒性劑量之桑椹萃取物加強抗癌藥 以及放射線殺死癌細胞株的效果，並探討其可能之細胞死亡機制。首 先以不同腫瘤之細胞株進行篩選，並以相對應的正常細胞株比較，用 無毒性濃度的桑椹萃取物(水萃物、多酚萃物與花青素萃物)合併不同 劑量的放射線或抗癌藥處理細胞，找出最佳合併治療條件，之後再進 一步探討其作用機制為何。分析的標的為對細胞的長短期毒性，細胞 死亡的型式，相關機制中訊息傳遞路徑重要蛋白質的表現量與活性的 改變。 第二年: 以動物實驗分別評估無毒性劑量的桑椹萃取物是否可於活 體加強抗癌藥以及放射線治療的效果，並探討其分子機制以及對腫瘤 血管新生與動物體發炎反應的影響。以第一年篩選之後證明有合併療 效的細胞株，進行tumor xenograft實驗，觀察桑椹萃取物是否有增強 化放療效果。活體實驗的結果可作為未來臨床應用的評估依據。 第三年: 以細胞及動物實驗分別評估無毒性劑量的桑椹萃取物抑制 化放療後癌細胞轉移的效果。細胞實驗將以Boyden chamber和 zymograph技術分析合併治療對癌細胞的侵入及移動的能力的影響。 活體實驗則採用動物轉移模式，將細胞由尾靜脈注射於nude mice，觀 察合併治療是否有抑制癌細胞轉移、侵襲的效果。Project