目的 探究牡荊素對鼻咽癌CNE-2細胞裸鼠移植瘤生長的抑制作用及其可能的調(diào)控機制。方法 將BALB/c裸鼠通過左側(cè)前肢腋窩下接種CNE-2細胞構(gòu)建鼻咽癌裸鼠成瘤模型，待模型構(gòu)建成功后隨機分為模型組、牡荊素組（5、10 mg/kg）、腺苷酸活化蛋白激酶（AMPK）激動劑組（AICAR，200 mg/kg）、牡荊素＋AMPK抑制劑組（Compound C，20 mg/kg），每組各10只。牡荊素組分別按照相應劑量ig；AICAR組ip 200 mg/kg AICAR；牡荊素＋Compound C組采取ig 10 mg/kg牡荊素的同時ip 20 mg/kg Compound C，以上各組連續(xù)給藥21 d。給藥結(jié)束后測定裸鼠移植瘤體積和質(zhì)量；蘇木素–伊紅（HE）染色觀察移植瘤組織病理學改變；TUNEL染色檢測腫瘤組織細胞凋亡情況；免疫組織化學檢測腫瘤組織微管相關(guān)蛋白輕鏈3（LC3）-II、泛素結(jié)合蛋白（p62）蛋白表達；免疫熒光檢測腫瘤組織LC3-II和半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）表達；Western blotting檢測腫瘤組織Bcl-2相關(guān)X蛋白（Bax）、B淋巴細胞瘤-2（Bcl-2）、Casapse-3蛋白及AMPK/UNC-51樣激酶1（ULK1）通路相關(guān)蛋白相對表達。結(jié)果 與模型組相比，牡荊素各劑量組、AICAR組腫瘤生長緩慢，腫瘤體積和質(zhì)量均顯著降低（P＜0.05）；腫瘤細胞凋亡率，Caspase-3、LC3-II、Bax/Bcl-2、p-AMPK/AMPK、p-ULK1/ULK1蛋白表達均顯著升高，p62蛋白表達均顯著降低（P＜0.05）。與牡荊素10 mg/kg組相比，牡荊素＋Compound C組腫瘤生長良好，腫瘤體積和質(zhì)量均增加（P＜0.05），腫瘤細胞凋亡率，Caspase-3、LC3-II、Bax/Bcl-2、p-AMPK/AMPK、P-ULK1/ULK1蛋白表達均顯著降低，p62蛋白表達均顯著升高（P＜0.05）。結(jié)論 牡荊素能夠抑制鼻咽癌CNE-2細胞裸鼠移植瘤生長，其機制與激活AMPK/ULK1通路介導的自噬，促進腫瘤細胞凋亡相關(guān)。

Objective To investigate the inhibitory effect of vitexin on the growth of nasopharyngeal carcinoma CNE-2 cells transplanted into nude mice and its possible regulatory mechanism. Methods BALB/c nude mice were inoculated with CNE-2 cells under the left forearm armpit to construct a nasopharyngeal carcinoma nude mice tumor model. After the model was successfully constructed, they were randomly divided into model group, vitexin group (5 and 10 mg/kg), AMPK agonist group (AICAR, 200 mg/kg), and vitexin + AMPK inhibitor group (Compound C, 20 mg/kg), with 10 mice in each group. Vitexin group was ig administered at corresponding doses, AICAR group received ip injection of 200 mg/kg AICAR, vitexin + Compound C group received 10 mg/kg vitexin by ig and ip injection of 20 mg/kg Compound C, and the above groups were continuously administered for 21 d. Measure the volume and mass of transplanted tumor in nude mice after administration. HE staining was used to observe the pathological changes of the transplanted tumor tissue, TUNEL staining was used to detect apoptosis in tumor tissue. Detection of LC3-II and p62 protein expression by immunohistochemical in tumor tissue, immunofluorescence detection of LC3-II and Caspase-3 expression in tumor tissue, Western blotting was used to detect the relative expression of Bax, Bcl-2, Casapse-3 proteins, and AMPK/ULK1 pathway related proteins in tumor tissue. Results Compared with the model group, the tumor growth was slow, tumor volume and mass were significantly reduced (P < 0.05), tumor cell apoptosis rate, the protein expression of Caspase-3, LC3-II, Bax/Bcl-2, p-AMPK/AMPK, p-ULK1/ULK1 were significantly increased, and p62 protein expression were significantly reduced (P < 0.05) in each dose group of vitexin. Compared with the 10 mg/kg group of vitexin, the vitexin + Compound C group showed good tumor growth, increased tumor volume and mass (P < 0.05), increased tumor cell apoptosis rate, the protein expression of Caspase-3, LC3-II, Bax/Bcl-2, p-AMPK/AMPK, p-ULK1/ULK1 were significantly decreased, while p62 protein expression were significantly increased (P < 0.05). Conclusion Vitexin can inhibit the growth of nasopharyngeal carcinoma CNE-2 cells transplanted into nude mice, and its mechanism is related to activating AMPK/ULK1 pathway mediated autophagy and promoting tumor cell apoptosis.

河南省高等學校重點科研項目（20B320117）