EFFECT AND MECHANISM OF PROTEASE INHIBITOR OPROZOMIB ON DOXORUBICIN SENSITIVITY OF HEPATOCELLULAR CARCINOMA CELLS

被引:0
作者
Qi, Feng [1 ]
Zheng, Sheng [2 ]
Hou, Lu [3 ]
Fu, Xinnian [4 ]
Wang, Xinxin [4 ]
Fu, Zhipeng [4 ]
Yang, Juan [2 ]
机构
[1] Jinzhou Med Univ, Affiliated Hosp 1, Dept Gen Surg, 2 Sect 5 Renmin St, Jinzhou 121000, Liaoning, Peoples R China
[2] Third Peoples Hosp Yunnan Prov, Dept Gastroenterol, 292,Beijing Rd, Kunming 650011, Yunnan, Peoples R China
[3] Dalian Med Univ, Hosp 2, Dept Gen Surg, 467 Zhongshan Rd, Dalian 116000, Liaoning, Peoples R China
[4] Dali Univ, Grad Sch Clin Med, 2 Hongsheng Rd, Dali 671000, Yunnan, Peoples R China
来源
ACTA POLONIAE PHARMACEUTICA | 2024年 / 81卷 / 02期
关键词
protease inhibitor; oprozomib; proapoptotic gene; hepatocellular carcinoma; doxorubicin; drug resistance; DNA TOPOISOMERASE-II; CANCER; BORTEZOMIB; SYSTEM; CARFILZOMIB; GENERATION; RESISTANCE; APOPTOSIS; SURVIVAL; GROWTH;
D O I
10.32383/appdr/187813
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to examine the impact of Oprozomib (OPZ), an oral second-generation proteasome inhibitor, on the sensitivity of hepatocellular carcinoma (HCC) cells to doxorubicin (DOX), a commonly used chemotherapy drug for the treatment of HCC. HCC cells were incubated with OPZ or DOX. Cell proliferation was assessed using MTT and colony formation assay, while cell migration and invasion were evaluated using scratch assay and Transwell assay. Cell apoptosis was measured using flow cytometry, and apoptosis-related molecules were determined through Western blot analysis. The proliferation, migration, and invasion of HCC cells were effectively suppressed by OPZ in a dose-dependent manner. This inhibition was achieved through the upregulation of pro-apoptotic genes, resulting in the promotion of apoptosis. Furthermore, OPZ significantly augmented the cytotoxicity and apoptosis induced by DOX. OPZ alone can effectively inhibit cell proliferation and induce apoptosis. OPZ can enhance DOX sensitivity and cellular apoptosis.
引用
收藏
页码:287 / 297
页数:11
相关论文
共 39 条
  • [1] Manuka honey enhanced sensitivity of HepG2, hepatocellular carcinoma cells, for Doxorubicin and induced apoptosis through inhibition of Wnt/β-catenin and ERK1/2
    Al Refaey, Heba R.
    Newairy, Al-Sayeda A.
    Wahby, Mayssaa M.
    Albanese, Chris
    Elkewedi, Mohamed
    Choudhry, Muhammad Umer
    Sultan, Ahmed S.
    [J]. BIOLOGICAL RESEARCH, 2021, 54 (01)
  • [2] Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets
    Bedford, Lynn
    Lowe, James
    Dick, Lawrence R.
    Mayer, R. John
    Brownell, James E.
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (01) : 29 - 46
  • [3] Approval summary for bortezomib for injection in the treatment of multiple myeloma
    Bross, PF
    Kane, R
    Farrell, AT
    Abraham, S
    Benson, K
    Brower, ME
    Bradley, S
    Gobburu, JV
    Goheer, A
    Lee, SL
    Leighton, J
    Liang, CY
    Lostritto, RT
    McGuinn, WD
    Morse, DE
    Rahman, A
    Rosario, LA
    Verbois, SL
    Williams, G
    Wang, YC
    Pazdur, R
    [J]. CLINICAL CANCER RESEARCH, 2004, 10 (12) : 3954 - 3964
  • [4] Sensitization of U937 leukemia cells to doxorubicin by the MG132 proteasome inhibitor induces an increase in apoptosis by suppressing NF-kappa B and mitochondrial membrane potential loss
    Cesar Ortiz-Lazareno, Pablo
    Bravo-Cuellar, Alejandro
    Manuel Lerma-Diaz, Jose
    Felipe Jave-Suarez, Luis
    Aguilar-Lemarroy, Adriana
    Ramiro Dominguez-Rodriguez, Jorge
    Gonzalez-Ramella, Oscar
    De Cellis, Ruth
    Gomez-Lomeli, Paulina
    Hernandez-Flores, Georgina
    [J]. CANCER CELL INTERNATIONAL, 2014, 14
  • [5] MicroRNA-101 modulates cisplatin chemoresistance in liver cancer cells via the DNA-PKcs signaling pathway
    Chai, Zongtao
    Yin, Xiaolan
    Chen, Jin
    Shi, Jie
    Sun, Juxian
    Liu, Chang
    Liu, Feng
    Cheng, Shuqun
    [J]. ONCOLOGY LETTERS, 2019, 18 (04) : 3655 - 3663
  • [6] The Bcl-2 family: roles in cell survival and oncogenesis
    Cory, S
    Huang, DCS
    Adams, JM
    [J]. ONCOGENE, 2003, 22 (53) : 8590 - 8607
  • [7] Development of proteasome inhibitors as research tools and cancer drugs
    Goldberg, Alfred L.
    [J]. JOURNAL OF CELL BIOLOGY, 2012, 199 (04) : 583 - 588
  • [8] Cytokines That Promote Periodontal Tissue Destruction
    Graves, Dana
    [J]. JOURNAL OF PERIODONTOLOGY, 2008, 79 (08) : 1585 - 1591
  • [9] Inhibitors for the Immuno- and Constitutive Proteasome: Current and Future Trends in Drug Development
    Huber, Eva Maria
    Groll, Michael
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (35) : 8708 - 8720
  • [10] Chemotherapy for hepatocellular carcinoma: current status and future perspectives
    Ikeda, Masafumi
    Morizane, Chigusa
    Ueno, Makoto
    Okusaka, Takuji
    Ishii, Hiroshi
    Furuse, Junji
    [J]. JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 2018, 48 (02) : 103 - 114