目的 研究墓頭回醋酸乙酯提取物環(huán)烯醚萜酯部位（PHEBB）的體內(nèi)外抗腫瘤作用及其機(jī)制。方法 硅膠柱色譜法精制PHEBB；反相高效液相色譜法分析PHEBB化學(xué)成分。MTT法檢測PHEBB對人腫瘤細(xì)胞KB、COLO-205、SGC-7901的抑制活性。采用小鼠移植性瘤模型研究PHEBB對小鼠S₁₈₀肉瘤、H₂₂肝癌的體內(nèi)抗腫瘤作用；免疫組化法研究PHEBB對腫瘤組織中相關(guān)基因表達(dá)的影響。結(jié)果 PHEBB主要成分均為環(huán)烯醚萜酯類，主要有desacetylisovaltratum、isovaltrate acetoxyhydrin。體外實(shí)驗(yàn)結(jié)果顯示，PHEBB對KB、COLO-205、SGC-7901等癌細(xì)胞均具有顯著抑制作用，IC₅₀在2.27～5.49 μg/mL。體內(nèi)實(shí)驗(yàn)顯示，PHEBB以60 mg/kg ip給予荷瘤小鼠，對S₁₈₀肉瘤的抑制率為45.5%，對H₂₂肝癌的抑制率為54.2%；免疫組化檢測結(jié)果顯示，PHEBB能上調(diào)小鼠H₂₂腫瘤組織中Bax表達(dá)，下調(diào)Bcl-2表達(dá)，且能降低腫瘤組織中微血管密度。結(jié)論 PHEBB抗腫瘤藥效物質(zhì)為環(huán)烯醚萜酯；其體內(nèi)外均具有一定抗腫瘤作用，且其抗腫瘤機(jī)制可能與誘導(dǎo)腫瘤細(xì)胞凋亡及抑制腫瘤微血管有關(guān)。

Objective To purify the iridoid ester fraction of ethyl acetate extract from Patriniae Radix (PHEBB), and to study the antitumor effect and mechanism in vivo and in vitro. Methods The silica gel column chromatography was used to purify the effective fraction. The chemical constituents of PHEBB were elucidated by RP-HPLC; MTT assay was used to study the inhibition of PHEBB on human oral epithelial cancer cells KB, human colon cancer cells COLO-255, and human gastric cancer cells SGC-7901; Mice transplanted S₁₈₀ and H₂₂ experiments were used to study the antitumor effect in vivo; The immunohistochemical method was used to study the effect of IEEAM on the expression of related genes in tumor tissue. Results The main effective components in PHEBB were desacetylisovaltratum and isovaltrate acetoxyhydrin, and they are both iridoid esters. The results of MTT showed that PHEBB had the significant inhibition on KB, COLO-205, and SGC-7901 cells, and the IC₅₀ values were within 2.27—5.49 μg/mL; The experiment of mice transplanted tumor showed that after ip injection with PHEBB at a dose of 60 mg/kg, there was an inhibitory rate of 45.5% on S₁₈₀ and 54.2% on H₂₂; The immunohistochemistry results showed that PHEBB could upregulate Bax expression in H₂₂ cells, decrease Bcl-2 expression, and reduce the microvascular density in tumor tissue. Conclusion The main components in PHEBB are iridoid esters, and have certain antitumor effect in vitro and in vivo; the antitumor mechanism of PHEBB might be associated with the induction of apoptosis and the inhibition of tumor microvessel.

浙江省自然科學(xué)基金資助項(xiàng)目（LY13C020003）；浙江省醫(yī)藥衛(wèi)生科技計(jì)劃（2012KYB137）