JDHY3 Inhibits Hypopharyngeal Carcinoma Cell Proliferation and Promotes Apoptosis by Inhibiting the PI3K/AKT Pathway


Дәйексөз келтіру

Толық мәтін

Аннотация

Background: Jieduhuayu No.3 (JDHY3) is a modified Chinese herbal formula beneficial for treating hypopharyngeal carcinoma (HC), but its pharmacological mechanism is unknown.

Objective: This study aimed to explore the mechanism of the herbal formula JDHY3 in inhibiting cell proliferation and promoting apoptosis in HC in vitro and in vivo.

Methods: In this study, HC cells were treated with cisplatin and different concentrations of JDHY3. The apoptosis rate was detected by flow cytometry. Western blotting was used to detect the proteins related to cell proliferation and apoptosis. Afterward, the xenograft mouse model was established and treated with cisplatin and JDHY3. Mouse tumour volume was measured, and the tumour tissues were assessed by HE staining and immunohistochemistry.

Results: JDHY3 significantly inhibited the proliferation of FaDu and Detroit-562 cells. In addition, JDHY3 significantly increased the apoptosis rate of HC cells and downregulated p-PI3K and p-Akt. In addition, JDHY3 upregulated the expression of the apoptosis-promoting proteins Bax, P53, and cleaved caspase-3. In addition, the expression of the antiapoptotic protein Bcl-2 was downregulated. Coincubation with SC79 attenuated the decrease in cell proliferation induced by JDHY3, further confirming that the proapoptotic effect of JDHY3 is associated with the inhibition of PI3K/Akt pathway activation.

Conclusions:The results of in vivo experiments showed that JDHY3 could effectively inhibit the proliferation of HC cells, and HE staining showed that JDHY3 reduced the invasion of HC cells. Immunohistochemistry showed that the expression of P53 and cleaved caspase-3 was significantly increased in the tissues of the JDHY3-treated group.

Авторлар туралы

Weili Dai

Department of Otolaryngology-Head Neck Surgery, Beijing Friendship Hospital, Capital Medical University

Email: info@benthamscience.net

Zhen Ni

Department of Otolaryngology, Lhasa People's Hospital

Email: info@benthamscience.net

Ganlin Zhang

Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University

Email: info@benthamscience.net

Jia Xu

Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University

Email: info@benthamscience.net

Xiaoyan Qin

Department of Otolaryngology, Lhasa People's Hospital

Email: info@benthamscience.net

Jingpeng Cao

Department of Otolaryngology, Lhasa People's Hospital

Email: info@benthamscience.net

Liangfa Liu

Department of Otolaryngology-Head Neck Surgery, Friendship Hospital, Capital Medical University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  1. Romanowska, K.; Sobecka, A.; Rawłuszko-Wieczorek, A.A.; Suchorska, W.M.; Golusiński, W. Head and neck squamous cell carcinoma: Epigenetic landscape. Diagnostics, 2020, 11(1), 34. doi: 10.3390/diagnostics11010034 PMID: 33375464
  2. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2017. CA Cancer J. Clin., 2017, 67(1), 7-30. doi: 10.3322/caac.21387 PMID: 28055103
  3. Zhu, G.; Peng, O.; Li, S.; Zhu, G.; Wang, S.; Liu, J.; Yin, D.; Peng, X.; Yang, T.; Tang, Q.; Yang, X. Three strategies for displaying the postcricoid space and pyriform sinus: A matched case-controlled study of 50 patients. Clin. Otolaryngol., 2019, 44(2), 187-190. doi: 10.1111/coa.13256 PMID: 30411859
  4. Tan, H.Y.; Sanudin, S.H.; Lum, S.G.; Wong, E.H.C. An unusual first presentation of hypopharyngeal carcinoma as thyroid abscess: Case report of a diagnostic challenge. Int. J. Surg. Case Rep., 2021, 81105723. doi: 10.1016/j.ijscr.2021.105723 PMID: 33713999
  5. Peng, X.; Liu, Y.; Zhu, S.; Peng, X.; Li, H.; Jiao, W.; Lin, P.; Zhang, Z.; Qiu, Y.; Jin, M.; Wang, R.; Kong, D. Co-targeting PI3K/Akt and MAPK/ERK pathways leads to an enhanced antitumor effect on human hypopharyngeal squamous cell carcinoma. J. Cancer Res. Clin. Oncol., 2019, 145(12), 2921-2936. doi: 10.1007/s00432-019-03047-2 PMID: 31620898
  6. Visini, M.; Giger, R.; Shelan, M.; Elicin, O.; Anschuetz, L. Predicting factors for oncological and functional outcome in hypopharyngeal cancer. Laryngoscope, 2021, 131(5), E1543-E1549. doi: 10.1002/lary.29186 PMID: 33098325
  7. Rong, L.; Li, Z.; Leng, X.; Li, H.; Ma, Y.; Chen, Y.; Song, F. Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway. Biomed. Pharmacother., 2020, 122, 109726. doi: 10.1016/j.biopha.2019.109726 PMID: 31918283
  8. Roudsari, N.M.; Lashgari, N.A.; Momtaz, S.; Abaft, S.; Jamali, F.; Safaiepour, P.; Narimisa, K.; Jackson, G.; Bishayee, A.; Rezaei, N.; Abdolghaffari, A.H.; Bishayee, A. Inhibitors of the PI3K/Akt/mTOR pathway in prostate cancer chemoprevention and intervention. Pharmaceutics, 2021, 13(8), 1195. doi: 10.3390/pharmaceutics13081195 PMID: 34452154
  9. Iksen, L.; Pothongsrisit, S.; Pongrakhananon, V. Targeting the PI3K/AKT/mTOR signaling pathway in lung cancer: An update regarding potential drugs and natural products. Molecules, 2021, 26(13), 4100. doi: 10.3390/molecules26134100 PMID: 34279440
  10. Zhou, R.; Liu, D.; Zhu, J.; Zhang, T. Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carci-noma. Medicine, 2020, 99(42), e22434. doi: 10.1097/MD.0000000000022434 PMID: 33080677
  11. Hsu, C.M.; Lin, P.M.; Tsai, Y.T.; Tsai, M.S.; Tseng, C.H.; Lin, S.F.; Yang, M.Y. NVP-BEZ235, a dual PI3K-mTOR inhibitor, suppresses the growth of FaDu hypopharyngeal squamous cell carcinoma and has a synergistic effect with Cisplatin. Cell Death Discov., 2018, 4(1), 57. doi: 10.1038/s41420-018-0060-7 PMID: 29760955
  12. Zhang, Y.; Cong, L.; He, J.; Wang, Y.; Zou, Y.; Yang, Z.; Hu, Y.; Zhang, S.; He, X. Photothermal treatment with EGFRmAb–AuNPs induc-es apoptosis in hypopharyngeal carcinoma cells via PI3K/AKT/mTOR and DNA damage response pathways. Acta Biochim. Biophys. Sin., 2018, 50(6), 567-578. doi: 10.1093/abbs/gmy046 PMID: 29718150
  13. Guo, Q.; Lin, J.; Liu, R.; Gao, Y.; He, S.; Xu, X.; Hua, B.; Li, C.; Hou, W.; Zheng, H.; Bao, Y. Review on the applications and molecular mechanisms of xihuang pill in tumor treatment. Evid. Based Complement. Alternat. Med., 2015, 2015, 1-10. doi: 10.1155/2015/854307 PMID: 26170886
  14. Yoon, B.K.; Lim, Z.Y.; Jeon, W.Y.; Cho, N.J.; Kim, J.H.; Jackman, J.A. Medicinal activities and nanomedicine delivery strategies for Brucea javanica oil and its molecular components. Molecules, 2020, 25(22), 5414. doi: 10.3390/molecules25225414 PMID: 33228061
  15. Wang, M.; Mao, D.; Li, H. Chinese medicine jiedu huayu granules reduce liver injury in rats by regulating t-cell immunity. Evid. Based Complement. Alternat. Med., 2019, 2019, 1-8. doi: 10.1155/2019/1873541 PMID: 31885638
  16. Qiu, H.; Mao, D.; Tang, N.; Long, F.; Zhang, R.; Wang, M.; Shi, Q.; Li, J.; Jiang, Q.; Chen, Y.; Wang, X. The underlying mechanisms of Jie-Du-Hua-Yu granule for protecting rat liver failure. Drug Des. Devel. Ther., 2019, 13, 589-600. doi: 10.2147/DDDT.S180969 PMID: 30809090
  17. Raine, C.H.; Stell, P.M.; Dalby, J. Squamous cell carcinomas of the posterior wall of the hypopharynx. J. Laryngol. Otol., 1982, 96(11), 997-1004. doi: 10.1017/S0022215100093427 PMID: 7130851
  18. Jol, J.K.A.D.; Quak, J.J.; de Bree, R.; Leemans, C.R. Larynx preservation surgery for advanced posterior pharyngeal wall carcinoma with free flap reconstruction: A critical appraisal. Oral Oncol., 2003, 39(6), 552-558. doi: 10.1016/S1368-8375(03)00037-X PMID: 12798397
  19. Kwon, D.I.; Miles, B.A. Hypopharyngeal carcinoma: Do you know your guidelines? Head Neck, 2019, 41(3), 569-576. doi: 10.1002/hed.24752 PMID: 30570183
  20. Li, Y.; Yang, G.; Li, M.; Tong, X. Nursing observation on the clinical efficacy and toxicity of lobaplatin compared with cisplatin in the treatment of locally advanced hypopharyngeal carcinoma based on intelligent ct imaging. J. Healthc. Eng., 2021, 2021, 1-11. doi: 10.1155/2021/9982888 PMID: 34306603
  21. Pavón, M.A.; Arroyo-Solera, I.; Céspedes, M.V.; Casanova, I.; León, X.; Mangues, R. uPA/uPAR and SERPINE1 in head and neck cancer: Role in tumor resistance, metastasis, prognosis and therapy. Oncotarget, 2016, 7(35), 57351-57366. doi: 10.18632/oncotarget.10344 PMID: 27385000
  22. Pavón, M.A.; Arroyo-Solera, I.; Téllez-Gabriel, M.; León, X.; Virós, D.; López, M.; Gallardo, A.; Céspedes, M.V.; Casanova, I.; López-Pousa, A.; Mangues, M.A.; Quer, M.; Barnadas, A.; Mangues, R. Enhanced cell migration and apoptosis resistance may underlie the asso-ciation between high SERPINE1 expression and poor outcome in head and neck carcinoma patients. Oncotarget, 2015, 6(30), 29016-29033. doi: 10.18632/oncotarget.5032 PMID: 26359694
  23. Bajou, K.; Peng, H.; Laug, W.E.; Maillard, C.; Noel, A.; Foidart, J.M.; Martial, J.A.; DeClerck, Y.A. Plasminogen activator inhibitor-1 pro-tects endothelial cells from fasl-mediated apoptosis. Cancer Cell, 2008, 14(4), 324-334. doi: 10.1016/j.ccr.2008.08.012 PMID: 18835034
  24. Spangle, J.M.; Roberts, T.M.; Zhao, J.J. The emerging role of PI3K/AKT-mediated epigenetic regulation in cancer. Biochim. Biophys. Acta Rev. Cancer, 2017, 1868(1), 123-131. doi: 10.1016/j.bbcan.2017.03.002 PMID: 28315368
  25. Mayer, I.A.; Arteaga, C.L. The PI3K/AKT pathway as a target for cancer treatment. Annu. Rev. Med., 2016, 67(1), 11-28. doi: 10.1146/annurev-med-062913-051343 PMID: 26473415
  26. Dai, W.; Jin, X.; Jiang, B.; Chen, W.; Ji, Z.; Xu, X.; Tang, M.; Dai, K.; Han, L. Elevated o-glcnacylation promotes malignant phenotypes of hypopharyngeal squamous cell carcinoma by stabilizing nrf2 through regulation of the pi3k/akt pathway. Anticancer. Agents Med. Chem., 2020, 20(16), 1933-1942. doi: 10.2174/1871520620666200615132435 PMID: 32538734
  27. Ju, S.H.; Tan, L.R.; Liu, P.W.; Tan, Y.L.; Zhang, Y.T.; Li, X.H.; Wang, M.J.; He, B.X. Scutellarin regulates osteoarthritis in vitro by inhibit-ing the PI3K/AKT/mTOR signaling pathway. Mol. Med. Rep., 2020, 23(1), 83. doi: 10.3892/mmr.2020.11722 PMID: 33236146
  28. Cao, P.; Liu, B.; Du, F.; Li, D.; Wang, Y.; Yan, X.; Li, X.; Li, Y. Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways. Thorac. Cancer, 2019, 10(3), 492-500. doi: 10.1111/1759-7714.12962 PMID: 30666790
  29. Wang, L.; Yang, H.; Wang, C.; Shi, X.; Li, K. Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway. Biomed. Pharmacother., 2019, 120109443. doi: 10.1016/j.biopha.2019.109443 PMID: 31541884
  30. Yang, J.; Li, X.; Yang, H.; Long, C. Oleanolic acid improves the symptom of renal ischemia reperfusion injury via the pi3k/akt pathway. Urol. Int., 2021, 105(3-4), 215-220. doi: 10.1159/000506778 PMID: 33291121
  31. Li, X.; Song, Y.; Zhang, P.; Zhu, H.; Chen, L.; Xiao, Y.; Xing, Y. Oleanolic acid inhibits cell survival and proliferation of prostate cancer cells in vitro and in vivo through the PI3K/Akt pathway. Tumour Biol., 2016, 37(6), 7599-7613. doi: 10.1007/s13277-015-4655-9 PMID: 26687646
  32. Dai, W.L.; Liu, X.T.; Bao, Y.N.; Yan, B.; Jiang, N.; Yu, B.Y.; Liu, J.H. Selective blockade of spinal D2DR by levo-corydalmine attenuates morphine tolerance via suppressing PI3K/Akt-MAPK signaling in a MOR-dependent manner. Exp. Mol. Med., 2018, 50(11), 1-12. doi: 10.1038/s12276-018-0175-1 PMID: 30429454

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