Objective: To investigate the effects of human telomerase reverse transcriptase (hTERT) on the growth of Capan-2 human pancreatic cancer cell and apoptosis.
Methods: Cell proliferation, apoptosis and cell cycle were analyzed by cell counting and flow cytometry. mRNA and protein expressions of hTERT, Bcl-2 and cyclooxygenase (COX)-2 were assessed by real time PCR and Western blot.
Results: Cell growth was significantly inhibited by 26.39 percent 24 h after hTERT-small interference RNA (siRNA) transfection (50 nmol/L) with a 100 percent silencing efficiency (P < 0.05). The inhibition rates of cell proliferation were 46.77 percent, 70.61 percent, 84.71 percent and 85.99 percent at 2, 3, 5 and 7 days after transfection, respectively (P < 0.001). Early and late apoptotic cells increased significantly (especially 24 h after transfection) (P < 0.001). The cell cycle was suppressed significantly as manifested by the increase of cells in the G0/G1 phase and the decrease of cells in the S phase and G2/M phase (P < 0.01). The expressions of Bcl-2 mRNA and COX-2 mRNA were inhibited significantly 48 h after transfection: the inhibition rates were 86.86 percent and 100 percent, respectively (P < 0.001). Levels of Bcl-2 protein were downregulated by 58.54 percent and 63.44 percent and the levels of COX-2 protein were downregulated by 50.06 percent and 82.77 percent at 48 h and 72 h after transfection, respectively.
Conclusion: Knockdown of hTERT by siRNA can inhibit the growth of Capan-2 cell. The inhibitory effect is associated with the downregulation of Bcl-2 and COX-2.
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http://dx.doi.org/10.1111/j.1751-2980.2010.00433.x | DOI Listing |
Biochim Biophys Acta Mol Basis Dis
December 2024
Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea; Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea. Electronic address:
Background: Oxaliplatin is a commonly used platinum-based chemotherapy drug for patients with pancreatic cancer (PC). Drug resistance is a major challenge in PC treatment, underscoring the urgent need for new approaches. Targeting DNA damage repair, one of the factors responsible for platinum resistance, is an attractive strategy to overcome drug resistance.
View Article and Find Full Text PDFFront Oncol
October 2024
Department of Radiation Oncology-Research, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration.
View Article and Find Full Text PDFJ Adv Res
September 2024
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China; The Chinese University of Hong Kong Chinese Medicine Specialty Clinic cum Clinical Teaching and Research Centre, School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:
J Immunother Cancer
April 2024
Lentigen Technology Inc., a Miltenyi Biotec Company, Gaithersburg, Maryland, USA
Background: Chimeric antigen receptor (CAR) T-cell therapy target receptor tyrosine kinase-like orphan receptor 1 (ROR1) is broadly expressed in hematologic and solid tumors, however clinically-characterized ROR1-CAR T cells with single chain variable fragment (scFv)-R12 targeting domain failed to induce durable remissions, in part due to the immunosuppressive tumor microenvironment (TME). Herein, we describe the development of an improved ROR1-CAR with a novel, fully human scFv9 targeting domain, and augmented with TGFβRIIDN armor protective against a major TME factor, transforming growth factor beta (TGFβ).
Methods: CAR T cells were generated by lentiviral transduction of enriched CD4 and CD8 T cells, and the novel scFv9-based ROR1-CAR-1 was compared with the clinically-characterized ROR1-R12-scFv-based CAR-2 in vitro and in vivo.
RSC Med Chem
November 2023
Chemistry, School of Environmental & Life Sciences, The University of Newcastle University Drive Callaghan NSW 2308 Australia
From lead 1, (-(4-((4-(3-(4-(3-methoxyphenyl)-1-1,2,3-triazol-1-yl)propyl)piperazin-1-yl)sulfonyl)-phenyl)acetamide), a S100A2-p53 protein-protein interaction inhibitor based on an modelling driven hypothesis, four focused libraries were designed and synthesised. Growth inhibition screening was performed against 16 human cancer cell lines including the pancreatic cell lines MiaPaCa2, BxPC3, AsPC-1, Capan-2, HPAC, PANC-1 and the drug resistant CFPAC1. Modification of 1's phenylacetamide moiety, gave with only modest pancreatic cancer activity.
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