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  • br Conclusions br Previous work from

    2020-08-28


    5. Conclusions
    Previous work from this laboratory demonstrated that light-trig-gered CO delivery by the photoCORM can attenuate antioxidant capa-city in human breast cancer 641-38-3 through inhibition of CBS and sensi-tizes such cells to doxorubicin and paclitaxel [10]. Sensitization of human ovarian cancer cells to cisplatin therapy through administration of CO now demonstrates the general concept of CBS inhibition as a treatment modality to overcome chemoresistance encountered in ovarian cancer therapy. Strategies that overcome cisplatin resistance may dramatically reduce the mortality of ovarian cancer [4]. Here we have presented that CO, delivered from a photoCORM, sensitizes es-tablished cisplatin-resistant cell lines to cisplatin. Furthermore, we have provided strong evidence that the effects of CO in circumventing che-motherapeutic drug resistance is at least in part mediated by the in-activation of endogenous CBS (as evidenced by the reduction in CTH, the direct metabolic product of CBS).
    Notes
    The authors declare no competing financial interests.
    Acknowledgments
    Financial support from the NSF grant DMR-1409335 (to PM) and Departmental funding from the Department of Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA is gratefully acknowledged. CJ acknowledges support from the NIH U01 grant HD087221. Statistical analysis by Ariel Wen, M.B.A. of the UCLA Anderson School of Management is gratefully acknowledged.
    Appendix A. Supplementary data
    References
    P. Szoleczky, D. Gero, K. Yanagi, G. Toro, I. Lopez-Garcia, V. Myrianthopoulos,
    Contents lists available at ScienceDirect
    International Journal of Biological Macromolecules
    Carboxypeptidase A4 promotes cell growth via activating STAT3 and ERK signaling pathways and predicts a poor prognosis in colorectal cancer
    a Department of Gastric Surgery, Fudan University Shanghai Cancer Center, 200032 Shanghai, China
    b The Second Affiliated Hospital of Fujian Medical University, 362000 Quanzhou, China
    c Department of Oncology, Shanghai Medical College, Fudan University, 200032 Shanghai, China
    d Department of Gastrointestinal Surgery, Beijing Hospital, 100730 Beijing, China
    e Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, 510080 Guangzhou, China
    Article history:
    Keywords:
    Carboxypeptidase A4
    Colorectal cancer
    STAT3 signaling pathway 
    Carboxypeptidase A4 (CPA4) is a novel cancer-related gene that is aberrantly expressed in various malig-nant tumors. However, the roles and mechanisms of CPA4 have not been explored in colorectal cancer (CRC). In this study, we investigated the functions and mechanisms by which CPA4 promotes CRC pro-gression. Quantitative real-time PCR (qRT-PCR) and western blot showed that CPA4 mRNA and CPA4 pro-tein levels were up-regulated in CRC compared to levels in adjacent normal tissue. Immunohistochemistry (IHC) results indicating high CPA4 levels were positively associated with poor prognoses. In addition, Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays demonstrated that CPA4 overexpression facilitated the growth of CRC cells, whereas CPA4 knockdown resulted in decreased prolif-eration, G1/S phase transition arrest, and apoptosis. Subcutaneous tumorigenesis was performed in nude mice to confirm the tumor-promoting effects of CPA4 in vivo. Western blot revealed that activation of the STAT3 and ERK pathways is one of the oncogenic functions of CPA4 in CRC. Accordingly, CPA4 promotes CRC cell growth via activating the STAT3 and ERK pathways and may be a prognostic factor or therapeutic target for CRC.
    1. Introduction
    Colorectal cancer (CRC) is the third most common malignant tumor and the third leading cause of death globally, with around 1,800,000 new cases and 861,000 deaths in 2018 [1]. According to data from the Chinese National Cancer Center, CRC is the fourth most common cancer in women and the fifth most common cancer in men [2]. CRC is a het-erogeneous disease with complex mechanisms of pathogenesis. Al-though clinicians have made great efforts to improve the comprehensive treatments available, the survival outcomes of CRC
    Correspondence to: H. Pan, Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, China.
    Correspondence to: Y. Guo, Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. E-mail addresses: [email protected] (H. Pan), [email protected]