Email this article Studies on the proliferation inhibition effects of TUA from Actinidia chinensis Radix on lung cancer xenografts in nude mice and its preliminary mechanism
Vol 5, Issue 2.1, 2021
VIEWS - 41 (Abstract) 31 (PDF)
Abstract
Objective: To investigate inhibitory effect of TUA (2β, 3β, 23-trihydroxy-urs-12-en-28-oic acid) isolated from Actinidia chinensis Radix on the lung cancer xenografts in nude mice and explore its preliminary mechanism. Methods: NCI-H460 cells were implanted into nude mice and the transplantation tumor block from nude mice of more than 2 generations was inoculated to the right armpits of BALB/c mice with dissecting needle to establish a lung cancer xenograft model. When the transplanted volume was about 50 mm3, the mice were randomly divided into 6 groups: (1) model group; (2) 10 mg·kg–1 cisplatin group; (3) 10 mg·kg–1 PDTC group; (4) TUA high dose group (30 mg·kg–1); (5) TUA middle dose group (12 mg·kg–1); (6) TUA low dose group (6 mg·kg–1). Administration approach was intratumoral injection. The effects of each group on the weight of transplanted tumor animals, the volume and weight of tumor were continuously observed for 14 days. Tumor volume growth curve was drawn and tumor inhibitory rate and index were calculated; HE staining was used to observe nude mice tumor tissue pathological changes. The effects of TUA on NF-κB signaling pathway related proteins were detected by immunohistochemistry and Western blot. Results: In vivo experiments showed that the transplanted tumors in nude mice became smaller compared with the models. With the increase of TUA dose, the tumor tissue became smaller and smaller, especially in high TUA dose (30 mg·kg–1). It had the similar size with the NF-κB inhibitor PDTC (10 mg·kg–1) group. HE dyeing observation results confirmed the degree of tumor necrosis and fission in TUA treated tumor tissues obviously decreased. Immunohistochemical results showed that comparing the TUA treatment group with the model group, p65 expression in tumor tissues was reduced, and expression of IκBα increased. Western blot results also showed that the NF-κB related p65 protein expression levels decreased, at the same time IκBα protein expression level increased; the apoptosis related proteins Survivin protein expression was depressed, Caspase-3 protein expression was promoted. Conclusion: TUA significantly inhibits the growth of lung transplantation tumor and its mechanism. It may be related to the decreasing the expression of p65, Survivin and increasing the expression of IκBα, Caspase-3 in tumor tissues.
Keywords
Full Text:
PDFReferences
1. Burris HA. Shortcomings of current therapies for non-small-cell lung cancer: Unmet medical needs. Oncogene 2009; 28(Suppl 1): 4–13.
2. Benlloch S, Alenda C, Galbis-Caravajal JM, et al. Expression of molecular markers in mediastinal nodes from resected stage I non-small-cell lung cancer (NSCLC): Prognostic impact and potential role as markers of occult micrometastases. Annals of Oncology 2009; 20(1): 91–97.
3. Song J, Sohn EJ, Kim B, et al. Inhibition of protein kinase C α/βII and activation of c-Jun NH2-terminal kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung cancer NCI-H460 cells. Bioorganic & Medicinal Chemistry Letters 2014; 24(4): 1188–1191.
4. Mishra BB, Tiwari VK. Natural products: An evolving role in future drug discovery. European Journal of Medicinal Chemistry 2011; 46(10): 4769–4807.
5. Li J, Huang R, Yao G, et al. Synthesis and biological evaluation of novel aniline-derived asiatic acid derivatives as potential anticancer agents. European Journal of Medicinal Chemistry 2014; 86(4): 175–188.
6. Zuo L, Wang Z, Fan Z, et al. Evaluation of antioxidant and antiproliferative properties of three Actinidia (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) extracts in vitro. International Journal of Moleclar Sciences 2011; 13(5): 5506–5518.
7. Zhang X, Wu J, Dou Y, et al. Asiatic acid protects primary neurons against C2 -ceramide-induced apoptosis. European Journal of Pharmacology 2012; 679(1-3): 51–59.
8. Cheng Q, Li H, Huang Z, et al. 2β, 3β, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) isolated from Actinidia chinensis Radix inhibits NCI-H460 cell proliferation by decreasing NF-κB expression. Chemico Biological Interactions 2015; 240: 1–11.
9. Lee H, Herrmann A, Deng J, et al. Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. Cancer Cell 2009; 15(4): 283–293.
10. Hu F, Qiao T, Xie X, et al. Knockdown of the inflammatory factor pentraxin-3 suppresses growth and invasion of lung adenocarcinoma through the AKT and NF-kappaB pathways. Journal of Biological Regulators & Homeostatic Agents 2014; 28(4): 649–657.
11. Luo J, Kamata H, Karin M. IKK/NF-kappaB signaling: Balancing life and death—A new approach to cancer therapy. Journal of Clinical Investigation 2005; 115(10): 2625–2632.
12. Bharti AC, Aggarwal BB. Chemopreventive agents induce suppression of nuclear factor-kappaB leading to chemosensitization. Annals of the New York Academy of Sciences 2002; 973(1): 392–395.
13. Rayet B, Gélinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene 1999; 18(49): 6938–6947.
14. Mehta HJ, Patel V, Sadikot RT. Curcumin and lung cancer—A review. Targeted Oncology 2014; 9(4): 295–310.
15. Qi C, Gao S, Li H, et al. The effect and mechanism of vinorelbine on cisplatin resistance of human lung cancer cell line A549 /DDP. Chinese Journal of Lung Cancer 2014; 17(2): 148–154.
16. Kaewpiboon C, Surapinit S, Malilas W, et al. Feroniellin A-induced autophagy causes apoptosis in multidrug-resistant human A549 lung cancer cells. International Journal of Oncology 2014; 44(4): 1233–1242.
17. Rousalova I, Banerjee S, Sangwan V, et al. Minnelide: A novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo. Plos One 2013; 8(10): e77411.
18. Tsao SM, Hsia TC, Yin MC. Protocatechuic acid inhibits lung cancer cells by modulating FAK, MAPK, and NF-κB pathways. Nutrition ＆ Cancer 2014; 66(8): 1331–1441.
19. Choi KE, Hwang CJ, Park MH, et al. Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. Toxins 2014; 6(8): 2210–2228.
20. Bai X, Wu Y, Wang T, et al. Expression of Survivin and Caspase-3 in cholangiocarcinoma and relationship with HBV infection. Journal of Harbin Medical University 2014; 48(1): 25–28.
21. Zhang S, Liu X, Du J, et al. Survivin-siRNA inhibits proliferation of lung cancer A549 cells and enhances their chemosensitity to cisplatin. Chinese Journal of Cancer Biotherapy 2009; 16(6): 583–587.
22. Lv L, An X, Li H, et al. Effect of miR-155 knockdown on the reversal of doxorubicin resistance in human lung cancer A549/dox cells. Oncology Letters 2016; 11(2): 1161–1166.
DOI: https://doi.org/10.24294/ti.v5.i2.1.1371
Refbacks
- There are currently no refbacks.
Copyright (c) 2021 Xiaohua Guo, Haibo Hu, Qi Jin, Hongliang Li, Qilai Cheng
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This site is licensed under a Creative Commons Attribution 4.0 International License.