该研究旨在考察灵芝孢子油番茄红素复合物（LZFQ）体内外抗肿瘤活性，探讨其对肿瘤细胞的作用机制。用MTT法对人非小细胞肺癌细胞（A549）、人胃癌细胞（BGC823）、人乳腺癌细胞（MCF-7）和人结肠癌细胞（HCT116）细胞活力进行检测，建立裸鼠移植瘤模型研究LZFQ的体内抑瘤作用，通过流式细胞术检测细胞凋亡变化及凋亡相关蛋白的表达，对其抗肿瘤机制进行初步探讨。体外细胞活力实验表明LZFQ对4种肿瘤细胞的生长均具有一定抑制作用，对A549细胞的抑制最明显（IC50=0.49 mg/mL）。流式细胞术实验表明，LZFQ可以浓度依赖性的诱导细胞凋亡。Western blot实验表明，LZFQ浓度依赖性地降低抑凋亡蛋白Bcl-2的水平、并提高促凋亡蛋白Bax及Caspase-3的水平。裸鼠移植瘤实验中，LZFQ给药剂量为2.00 g/kg（高剂量组）、1.00 g/kg（中剂量组）和0.50 g/kg（低剂量组）时，对裸鼠移植瘤的抑制率分别为60.58%、51.92%和43.27%，其中高、中、低剂量组与模型组比较均有显著差异（p<0.01）。机制研究表明，LZFQ可以浓度依赖性诱导细胞凋亡，并通过影响凋亡相关蛋白的表达诱导细胞凋亡。该研究结果表明LZFQ具有一定的抗肿瘤作用，可为灵芝孢子油类产品的研发提供实验依据。

The in vitro and in vivo antitumor activities of Ganoderma lucidum spore oil-lycopene complex (LZFQ), and its mechanism of action in A549 cells were investigated. The MTT method was used to measure the viability of human non-small cell lung cancer cells (A549), human gastric cancer cells (BGC823), human breast cancer cells (MCF-7) and human colon cancer cells (HCT116). A nude mouse transplanted tumor model was established to study the in vivo inhibitory effect of LZFQ on tumor. The changes in apoptosis and the expression of apoptosis-related proteins were examined by flow cytometry, and its anti-tumor mechanism was preliminarily explored. In vitro cell viability experiments showed that LZFQ had certain inhibitory effects on the growth of four kinds of tumor cells, with its inhibition on A549 cells being the greatest (IC50=0.49 mg/mL). Flowcytometry experiments showed that LZFQ could induce apoptosis in a concentration-dependent manner. Western blot experiments showed that LZFQ could reduced the level of anti-apoptotic protein Bcl-2 and increased the levels of pro-apoptotic proteins Bax and Caspase-3 in a concentration-dependent manner. The nude mice transplanted tumor experiments showed that when LZFQ was administered at doses of 2.00 g/kg (high dose group), 1.00 g/kg (medium dose group) and 0.50 g/kg (low dose group), the inhibition rates of transplanted tumor in nude mice were 60.58%, 51.92% and 43.27% respectively, with significant differences detected between the high-/medium-/low-dose groups and the model group (p<0.01). Mechanism studies showed that LZFQ could induce apoptosis in a concentration-dependent manner, and induce apoptosis by affecting the expressions of apoptosis-related proteins. The research results show that LZFQ has a certain anti-tumor effect, which can provide an experimental basis for the research and development of Ganoderma lucidum spore oil products.

科技部“重大新药创制”重大科技专项（2011ZX09307-002）