Study on the inhibitory effect of Alcohol extract of Inonotus Obliquus on the development and progression of gastric cancer and its molecular mechanism
WANG Wei1 ZHOU Zhongguang2▲ YANG Jing1 LIU Xu3 TIAN Ming3 QIAO Yu4 ZHONG Lili5
1.Teaching and Research Department of Pathology, Basic Medical College, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
2.Teaching and Research Department of Histoembryology, Basic Medical College, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
3.Experiment and Training Center, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
4.Teaching and Research Department of Shanghan, Basic Medical College, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
5.Department of Pathology, the First Clinical Medical College, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China
Abstract：Objective To investigate the inhibitory effect of Alcohol extract of Inonotus Obliquus (Alcohol extract of IO) on transplanted tumor of gastric cancer BGC-823 in nude mice, and speculate the relationship between the mechanism and PI3K/AKT pathway. Methods Forty-eight nude mice were used to establish gastric cancer models by heterotopic transplantation. After modeling, they were randomly divided into Alcohol extract of IO high-dose group (3 mg/g), middle-dose group (1 mg/g) and low-dose group (0.75 mg/g), negative control group (hydroxymethyl cellulose sodium lavage), model group (no drug), positive control group (Capecitabine lavage, 0.5 mg/g). according to the random number table method, with 8 mice in each group. Mice were sacrificed after 14 days of intragastric administration, tumor tissues were stripped and tumor inhibition rate was calculated by weighing. The morphological changes of tumor tissues after drug intervention were observed under light microscope and electron microscope. The expressions of 4E-BP1, p27kip1, Bcl-2, Bax and caspase-3 were detected by immunohistochemistry. The expressions of Phosphatase gene (PTEN), phosphatidylinositol-3-hydroxykinase (PI3K), protein kinase (AKT), and target of rapamycin (mTOR) were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of PI3K and p-AKT were detected by Western blot. Results Compared with the negative control group and model group, the weight of tumor were reduced in Alcohol extract of IO group (P < 0.05), the growth in each Alcohol extract of IO groups was inhibited (P < 0.05). In the each Alcohol extract of IO groups, tumor necrosis, apoptosis and organelle destruction were more obvious (P < 0.05). Compared with the negative control group and model group, the average optical density of Bcl-2 in each Alcohol extract of IO groups was decreased, the average optical density of 4E-Bp1, p27kip1, Bax and caspase-3 was increased (P < 0.05). RT-PCR detect results showed that, the expression of PTEN in each Alcohol extract of IO groups was higher than that in the negative control group and model group, and was lower than that in the positive control group (P < 0.05); the expressions of mTOR, PI3K and AKT in the each Alcohol extract of IO groups were higher than those in the positive control group, and were lower than those in the negative control group and model group (P < 0.05). Western blot detect results showed that, the expressions of PI3K and p-AKT protein in each Alcohol extract of IO groups were lower than those in negative control group and model group, and were higher those that in the positive control group (P < 0.05). Conclusion Alcohol extract of IO has obvious inhibitory effect on gastric cancer, and its mechanism may be related to PI3K/AKT pathway and its upstream and downstream factors.
王蔚1 周忠光2▲ 杨婧1 刘旭3 田明3 乔羽4 仲丽丽5. 桦褐孔菌醇提物抑制胃癌发生发展的作用及分子机制研究[J]. 中国医药导报, 2020, 17(14): 8-13.
WANG Wei1 ZHOU Zhongguang2▲ YANG Jing1 LIU Xu3 TIAN Ming3 QIAO Yu4 ZHONG Lili5. Study on the inhibitory effect of Alcohol extract of Inonotus Obliquus on the development and progression of gastric cancer and its molecular mechanism. 中国医药导报, 2020, 17(14): 8-13.
[1] Chan WL，Lam KO，Lee VHF，et al. Gastric Cancer-From Aetiology to Management：Differences Between the East and the West [J]. Clin Oncol，2019，31（8）：570-577.
[2] 李卫威，智晓玉，胡毅.晚期胃癌的治疗进展[J/OL].解放军医学院学报：1-5[2019-09-03].
[3] 李荣庚，章红权，曾志华.腹腔镜全胃切除联合D2淋巴结清扫术治疗进展期胃癌的疗效[J].上海医药，2019，40（15）：35-37.
[4] 吴建春，徐静，殷晓聆，等.中草药调节活性氧抗肿瘤的研究进展[J].中华中医药杂志，2019，34（4）：1589-1594.
[5] 部丽丽.制备HPLC法分离纯化桦褐孔菌醇的研究[D].上海：上海师范大学，2018.
[6] 孙跃胜，窦巩昊，陈恩德，等.胃癌病灶内幽门螺杆菌感染与病理特征、凋亡侵袭基因和PI3K/AKT信号通路的关系[J].中国微生态学杂志，2019，31（6）：666-669，676.
[7] 齐亭娟，周玉柏，曾毅.桦褐孔菌活性成分及药理作用的研究进展[J].智慧健康，2018，4（24）：50-53.
[8] Han YQ，Nan SJ，Fan J，et al. Inonotus obliquus polysaccharides protect against Alzheimer′s disease by regulating Nrf2 signaling and exerting antioxidative and antiapoptotic effects [J]. Int J Biol Macromol，2019，131：769-778.
[9] Duru KC，Kovaleva EG，Danilova IG，et al. The pharmacological potential and possible molecular mechanisms of action of Inonotus obliquus from preclinical studies [J]. Phytother Res，2019，33（8）：1966-1980.
[10] 赵卓卓，冉棋，丁辉，等.桦褐孔菌醇研究进展[J].食用菌学报，2018，25（4）：121-129.
[11] Yan L，Wenting Z，Chun C，et al. Inotodiol protects PC12 cells against injury induced by oxygen and glucose deprivation/restoration through inhibiting oxidative stress and apoptosis[J]. J Appl Biomed，2018， 16（2）.
[12] 李根培，朴惠善，陈兰仙.1桦褐孔菌乙醇提取物抗肿瘤活性的实验研究[J].求医问药：下半月刊，2012（2）：12.
[13] 白杨，叶龙，李晓京，等.桦褐孔菌醇对人卵巢癌SKOV3细胞增殖和凋亡的影响[J].实用妇产科杂志，2013，29 （6）：441-444.
[14] 王李俊，杨琴，王飞，等.桦褐孔菌醇诱导人乳腺癌MCF-7细胞凋亡的分子机制研究[J].中草药，2016，3（6）：970-973.
[15] Zhang SD，Yu L，Wang P，et al. Inotodiol inhibits cells migration and invasion and induces apoptosis via p53-dependent pathway in HeLa cells [J]. Phytomedicine，2019，60：152957.
[16] 池苗苗，王亚坤，谢长生.南方红豆杉水提物通过PI3K/AKT/mTOR信号通路调控HER2阳性胃癌移植瘤生长实验研究[J].浙江中西医结合杂志，2019，29（3）：176-180，259.
[17] 石燕燕，李树才，孙军.人参皂苷Rg3通过PI3K/AKT信号系统调控CaM基因表达促进胃癌BGC-823细胞的凋亡[J].中国肿瘤生物治疗杂志，2018，25（6）：590-594.
[18] 马志恒，陈建新，蒋海存，等.p-AKT，p-ERK在胃癌组织中表达及其意义[J].中华保健医学杂志，2016，18（4）：274-277.
[19] 程玉，李春辉，刘海旺，等.Akt1信号通路在胃癌组织中的表达及意义[J].广东医学，2015，36（4）：560-562.
[20] Singh SS，Yap WN，Arfuso F，et al. Targeting the PI3K/AKT signaling pathway in gastric carcinoma： A reality for personalized medicine [J]. World J Gastroenterol，2015， 21（43）：12261-12273.
[21] Sun R，Cheng E，Velásquez C，et al. Mitosis-related phosphorylation of the eukaryotic translation suppressor 4E-BP1 and its interaction with eukaryotic translation initiation factor 4E （eIF4E） [J]. J Biol Chem，2019，294（31）：11840-11852.
[22] Li J，Liu WJ，Hao HL，et al. Rapamycin enhanced the antitumor effects of doxorubicin in myelogenous leukemia K562 cells by downregulating the mTOR/p70S6K pathway [J]. Oncol Let，2019，18（3）：2694-2703.
[23] Subbarayan S，Subramanian S，Senthil KN. Recombinant Pierisin-5 Induces Apoptosis and Differential Expression of Bcl-2，Bax，and p53 in Human Cancer Cells [J]. DNA and Cell Biology，2019，38（8）：773-785.
[24] 陈昱文.健脾补土组方对体外神经元低氧/复氧后凋亡及PI3K、AKT、caspase3、caspase8表达的影响[D].长沙：湖南中医药大学，2017.
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