探討新型C/L/H標靶藥物對體內乳癌之抗癌機制

臨床的抗癌藥物因缺乏選擇性，因此，在化療藥物的過程中常引發強烈副作用。近期，微脂質體的發展能夠應用於抗腫瘤的藥物治療，微脂質體能夠提高藥物的傳送，從而增加腫瘤攝取藥物和降低正常組織的副作用。 LC是一個全新設計的微脂質體，其主要特點是通過非共價結合的吸附蛋白，能保護蛋白質活性，並且LC帶正電荷而提高藥物的傳遞效率。在傳統醫學中，薑黃素為多酚純化物，已知對於人體大部分的癌細胞都有抗腫瘤的抑制效果、抗氧化及抗血管生新生作用等。賀癌平(Herceptin)，是用在臨床治療具有Her2表達乳癌的單株抗體。本研究的目的是探討新的靶靶治療藥物在SKBR3乳腺癌細胞體內的抗腫瘤作用。實驗設計在LC外吸附上賀癌平(Herceptin)及脂質層包覆薑黃素作為新的標靶藥物（C / L / H complex）。利用免疫組織化學染色法（ IHC ）染色，觀察蛋白的表現量。實驗結果顯示，在C / L / H複合物顯著抑制血管形成和血管新生因子的表達，包含血管內皮生長因子(VEGF)，血管內皮生長因子受體1 (VEGFR1)和血管內皮生長因子受體2(VEGFR2)。此外，C / L / H複合物增強細胞凋亡，促使 caspase -3的表達量增加，但降低了PCNA的表達量，抑制腫瘤細胞的增生。 結果發現C / L / H複合物治療組較賀癌平(Herceptin)治療組具有更多的抗腫瘤作用並且可以有效抑制腫瘤的血管新生作用。總結，C / L / H複合物能增強藥物傳送和抗腫瘤的作用。因此， C / L / H複合物具有高度潛力發展出新的腫瘤標靶藥物。

In clinical, most chemotherapy drugs are without selectivity between malignant and normal tissues that cause many side effects in circulation. In recently, the liposome is developed as a tool to carry anti-tumor drugs for therapy. This method is able to enhance the drugs delivery, which increase tumor uptake drugs and reduce side effects in normal tissues. LC is a new designed liposome, and the major characteristic of LC is binding target protein through non-covalent conjugation to protect protein activity. The LC also contains positive charge that enhances drug delivery efficiently. In traditional medicine, the curcumin, a polyphenol compound, is used in a variety of diseases through its therapeutic effects such as anti-tumor, anti-oxidant, anti- angiogenesis. Herceptin, Trastuzumab, is a monoclonal antibody using in clinical therapy. The purpose of this study was to investigate the anti-tumor effects of new targeting therapy drug in SKBR3 human breast cancer in vivo. We had used LC absorption with Herceptin and encapsulated Curcumin as the new targeting drug C/L/H complex to treat SKBR3 tumor in vivo. And several protein expressions were detected by Immunohistochemistry (IHC) staining. The data showed that the C/L/H significantly suppressed the vessels formation and angiogenesis marker expression on VEGF, VEGF receptor 1 and VEGF receptor 2 after treatment. Moreover, the C/L/H complex increased apoptosis marker, activation caspase-3, expression but reduced the PCNA proliferation marker expression. In conclusion, the C/L/H complex had more anti-tumor effects and inhibited angiogenesis than Herceptin only, C/L/I, C+H+L and C/L/CD20. The C/L/H complex enhanced the drug delivery and anti-tumor effects. Consequently, C/L/H complex has a highly potential to develop as a tumor targeting drug.