scholarly journals Phospho-valproic acid (MDC-1112) reduces pancreatic cancer growth in patient-derived tumor xenografts and KPC mice: enhanced efficacy when combined with gemcitabine

2019 ◽  
Vol 41 (7) ◽  
pp. 927-939 ◽  
Author(s):  
Dingyuan Luo ◽  
Matthew G Digiovanni ◽  
Ran Wei ◽  
Joseph F Lacomb ◽  
Jennie L Williams ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Valproic Acid ◽  
Pancreatic Tumor ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Tumor Xenograft ◽  
Xenograft Growth ◽  
Kpc Mice ◽  
Tumor Xenograft Growth

Abstract New chemotherapeutic agents are needed for pancreatic cancer (PC). We have previously shown that phospho-valproic acid (MDC-1112) is effective in cell-line xenografts of PC. Here, we explored whether MDC-1112 is effective in additional clinically relevant animal models of PC and whether MDC-1112 enhances the anticancer effect of clinically used chemotherapeutic agents. MDC-1112 alone strongly reduced patient-derived pancreatic tumor xenograft growth, and extended survival of LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) mice. In both models, MDC-1112 inhibited STAT3 activation and its downstream signals, including Bcl-xL and cyclin D1. In human PC cell lines, P-V enhanced the growth inhibitory effect of gemcitabine (GEM), Abraxane and 5-FU, but not that of irinotecan. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of MDC-1112/GEM combination. Furthermore, MDC-1112 enhanced GEM’s effect on colony formation, apoptosis, cell migration, and cell invasion. In vivo, MDC-1112 and GEM, given alone, reduced patient-derived pancreatic tumor xenograft growth by 58% and 87%, respectively; whereas MDC-1112/GEM combination reduced tumor growth by 94%, inducing tumor stasis. In conclusion, MDC-1112 should be further explored as a potential agent to be used in combination with GEM for treating PC.

scholarly journals Circular RNA CDR1as Exerts Oncogenic Properties Partially through Regulating MicroRNA 641 in Cholangiocarcinoma

2020 ◽  
Vol 40 (15) ◽  
Author(s):  
Dingyang Li ◽  
Zhe Tang ◽  
Zhiqiang Gao ◽  
Pengcheng Shen ◽  
Zhaochen Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Target Genes ◽  
Circular Rna ◽  
Tumor Xenograft ◽  
Mrna Levels ◽  
Cell Behaviors ◽  
Xenograft Growth ◽  
Tumor Xenograft Growth

ABSTRACT It has been found that the circular RNA (circRNA) CDR1as is upregulated in cholangiocarcinoma (CCA) tissues. In this study, we tried to explore the roles of CDR1as in CCA. CDR1as was overexpressed or knocked down in human CCA cells to assess the effects of CDR1as on cell behaviors and tumor xenograft growth. In vitro, the CDR1as level was significantly increased in CCA cell lines. The results showed that CDR1as promoted the cell proliferation, migration, invasion, and activation of the AKT3/mTOR pathway in CCA cells. Moreover, miR-641, a predicted target microRNA (miRNA) of CDR1as, could partially reverse the effects of CDR1as on cell behaviors in CCA cells. Furthermore, CDR1as improved tumor xenograft growth, and it could be attenuated by miR-641 in vivo. Additionally, CDR1as expression was inversely correlated with miR-641 in CCA cells, and miR-641 could directly bind with CDR1as and its target genes, the AKT3 and mTOR genes. Mechanistically, CDR1as could bind with miR-641 and accelerate miR-641 degradation, which possibly leads to the upregulation of the relative mRNA levels of AKT3 and mTOR in RBE cells. In conclusion, our findings indicated that CDR1as might exert oncogenic properties, at least partially, by regulating miR-641 in CCA. CDR1as and miR-641 could be considered therapeutic targets for CCA.

scholarly journals Neutralization of Adrenomedullin Inhibits the Growth of Human Glioblastoma Cell Lines in Vitro and Suppresses Tumor Xenograft Growth in Vivo

2002 ◽  
Vol 160 (4) ◽  
pp. 1279-1292 ◽  
Author(s):  
L'Houcine Ouafik ◽  
Samantha Sauze ◽  
Françoise Boudouresque ◽  
Olivier Chinot ◽  
Christine Delfino ◽  
...  
Keyword(s):  
Cell Lines ◽  
Tumor Xenograft ◽  
Glioblastoma Cell ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cell ◽  
Xenograft Growth ◽  
Tumor Xenograft Growth ◽  
Glioblastoma Cell Lines

241 Small Molecule Inhibitors Xmd8-92 and Pv1019 Inhibit Pancreatic Tumor Xenograft Growth via a DCLK1 Dependent Mechanism

2013 ◽  
Vol 144 (5) ◽  
pp. S-53
Author(s):  
Sripathi M. Sureban ◽  
Dongfeng Qu ◽  
Parthasarathy Chandrakesan ◽  
Randal May ◽  
Nathaniel Weygant ◽  
...  
Keyword(s):  
Small Molecule ◽  
Pancreatic Tumor ◽  
Small Molecule Inhibitors ◽  
Tumor Xenograft ◽  
Xenograft Growth ◽  
Tumor Xenograft Growth ◽  
Dependent Mechanism

XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism

2014 ◽  
Vol 351 (1) ◽  
pp. 151-161 ◽  
Author(s):  
Sripathi M. Sureban ◽  
Randal May ◽  
Nathaniel Weygant ◽  
Dongfeng Qu ◽  
Parthasarathy Chandrakesan ◽  
...  
Keyword(s):  
Pancreatic Tumor ◽  
Tumor Xenograft ◽  
Xenograft Growth ◽  
Tumor Xenograft Growth ◽  
Dependent Mechanism

scholarly journals Proscillaridin A is cytotoxic for glioblastoma cell lines and controls tumor xenograft growth in vivo

Oncotarget ◽  
2014 ◽  
Vol 5 (21) ◽  
pp. 10934-10948 ◽  
Author(s):  
Emilie Denicolaï ◽  
Nathalie Baeza-Kallee ◽  
Aurélie Tchoghandjian ◽  
Manon Carré ◽  
Carole Colin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Tumor Xenograft ◽  
Glioblastoma Cell ◽  
Xenograft Growth ◽  
Proscillaridin A ◽  
Tumor Xenograft Growth ◽  
Glioblastoma Cell Lines

Astragaloside IV enhanced carboplatin sensitivity in prostate cancer by suppressing AKT/NF-κB signaling pathway

2020 ◽  
Author(s):  
Yi He ◽  
Qimei Zhang ◽  
Huan Chen ◽  
Qingxi Guo ◽  
Liming Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Tumor Xenograft ◽  
Prostate Cancer Cell Lines ◽  
Xenograft Growth ◽  
Tumor Xenograft Growth

In our study, we explored the effect of AgIV on carboplatin chemotherapy in prostate cancer cell lines in vitro and in vivo. Cell viability assay, colony formation assay, flow cytometry, western blot, immunohistochemistry (IHC), immunofluorescence and tumor xenograft growth assay were conducted. We found that AgIV significantly decreased the half maximal inhibitory concentration (IC50) of carboplatin in prostate cancer cell lines LNCap and PC-3. Moreover, AgIV enhanced the effect of carboplatin in suppressing colony formation and inducing cell apoptosis. A low dose carboplatin treatment upregulated N-cadherin and Vimentin expression and downregulated E-cadherin expression, but this effect was abolished by combining with AgIV. Carboplatin treatment increased the levels of p-AKT and p-p65 and decreased p-IκBα, but AgIV treatment suppressed this. In addition, AgIV synergized with carboplatin to suppress tumor xenograft growth of PC-3 cells, and decreased pAKT and p-p65 levels in vivo. In summary, our results suggested that AgIV enhanced carboplatin sensitivity in prostate cancer cell lines by suppressing AKT/NF-кB signaling, thus suppressed EMT induced by carboplatin. Our findings provided a new mechanism for AgIV in overcoming drug resistance of platinum-based chemotherapy, and suggested a potential combination therapy of AgIV and carboplatin in prostate cancer.

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