CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo

He, Xingxing; Zhang, Yu-Nan; Yan, Junwei; Yan, Jingjun; Wu, Qian; Song, Yufang

doi:10.1007/s13277-015-3857-5

Cited by 21 publications

(20 citation statements)

References 35 publications

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“…Subsequently, the mice were sacrificed and the livers were photographed and examined. Resected tumor tissues from xenograft mice and primary HCC mice were then tested by hematoxylin and eosin (HE), immunohistochemistry and TUNEL staining as described previously by us [2, 25, 26]. …”

Section: Methodsmentioning

confidence: 99%

Gold nanoparticles delivered miR-375 for treatment of hepatocellular carcinoma

et al. 2016

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MiR-375 is a tumor suppressor miRNA that is downregulated in hepatocellular carcinoma (HCC). However, due to the lack of effective delivery strategies, miR-375 replacement as a therapy for HCC has not been investigated. In the present study, we have developed a straightforward strategy to deliver miR-375 into HCC cells by assembling miR-375 mimics on the surface of AuNPs and forming AuNP-miR-375 nanoparticles. AuNP-miR-375 exhibits high cellular uptake and preserves miR-375′s activities to suppress cellular proliferation, migration/invasion, and colony formation, and to induce apoptosis in HCC cells. Furthermore, AuNP-delivered miR-375 efficiently downregulated its target genes through RNA interference. In primary and xenograft tumor mouse models, AuNP-miR-375 showed high tumor uptake, therapeutic efficacy, and no apparent toxicity to the host mice. In conclusion, our findings indicate that AuNPs is a reliable strategy to deliver miR-375 into HCC cells and tissue, and that AuNP-miR-375 has the potential in the clinic for treatment of unresectable HCC.

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Section: Methodsmentioning

confidence: 99%

Gold nanoparticles delivered miR-375 for treatment of hepatocellular carcinoma

et al. 2016

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“…In the present study, SW579 cells (carrying p53 mutations) were treated with a small-molecule agent CP-31398, which induces the desired phenotypic change (apoptosis and proliferation inhibition) in cancer cells with p53 mutations (29,30). CP-31398 caused notably decreased viability of SW579 cells (31).…”

Section: Discussionmentioning

confidence: 92%

Potential synergistic effects of sorafenib and CP‑31398 for treating anaplastic thyroid cancer with p53 mutations

Lin

Huang

et al. 2020

Oncol Lett

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Thyroid cancer is the most commonly diagnosed endocrine cancer. Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer and has a poor prognosis. Loss of p53 function has been reported to lead to poorly differentiated thyroid tumors; therefore, mutant p53 protein can be considered a crucial therapeutic target in patients with ATC. Sorafenib, a multi-kinase inhibitor, has been approved for the treatment of metastatic and differentiated thyroid cancer. Combined targeted therapy, including sorafenib, may be clinically significant for patients with ATC harboring p53 mutations. In the present study, CP-31398, a p53-restoring agent, was used to improve the therapeutic efficacy of sorafenib in SW579 cells, an ATC cell line harboring p53 mutations. The molecular function of CP-31398 was evaluated using western blot analysis and a luciferase reporter assay. The decreased viability of SW579 cells, following CP-31398 treatment, was augmented by sorafenib, and CP-31398 enhanced the antimitogenic effect of sorafenib; thus, sorafenib and CP-31398 synergistically inhibited the growth of SW579 cells. These results indicate a potential clinical application of CP-31398 for patients with ATC harboring p53 abnormalities, since these individuals generally respond poorly to sorafenib alone.

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“…Consistent with previous observations, we observed increased p53 levels and a decrease in cell cycle (cyclin D1, cyclin A) and proliferation biomarkers (PCNA) in treated tumors. Invitro and invivo studies have clearly shown that CP can restore the function of mutant p53 and also induce p53 signalling in wild type p53 expressing cells (18, 41–42). Our results clearly demonstrate that administration of CP suppresses urothelial tumorogeneis that occurs through inactivation of p53.…”

Section: Discussionmentioning

confidence: 99%

“…Our results clearly demonstrate that administration of CP suppresses urothelial tumorogeneis that occurs through inactivation of p53. While mutation of the p53 is a frequent event, half of the tumors still have normal p53 or that might have been inactivated by alternate mechanisms such as mdm2 overexpression (43) , CP with its potential to function in both p53 mutant and wildtype tumors has a broader application (18, 41–42). Although the molecular mechanism of p53 inactivation is different in SV40T mice compare to human tumors our results provide clear evidence that targeting p53 using cp can result in significant advantage in preventing urothelial tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Targeting mTOR and p53 Signaling Inhibits Muscle Invasive Bladder Cancer In Vivo

Madka

Mohammed

et al. 2016

Cancer Prevention Research

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Urothelial tumors, accompanied by mutations of the tumor suppressor protein TP53 and dysregulation of mTOR signaling, are frequently associated with aggressive growth and invasiveness. We investigated whether targeting these two pathways would inhibit urothelial tumor growth and progression. Six-week-old transgenic UPII-SV40T male mice (n=15/group) were fed control diet (AIN-76A) or experimental diets containing mTOR inhibitor (rapamycin, 8 or 16 ppm), p53 stabilizing agent (CP31398 [CP], 150 ppm), or a combination. Mice were euthanized at 40 weeks of age. Urinary bladders were collected and evaluated to determine tumor weight and histopathology. Each agent alone, and in combination, significantly inhibited tumor growth. Treatment with rapamycin alone decreased tumor weight up to 67% (p<0.0001). Similarly, CP showed ~77% (p<0.0001) suppression of tumor weight. The combination of low-dose rapamycin and CP led to ~83% (p<0.0001) inhibition of tumor weight. There was no significant difference in tumor weights between rapamycin and CP treatments (p>0.05). However, there was a significant difference between 8 ppm rapamycin and the combination treatment. Tumor invasion was also significantly inhibited in 53% (p<0.005) and 66% (p<0.0005) mice after 8 ppm and 16 ppm rapamycin respectively. While tumor invasion was suppressed in 73% (p<0.0001) mice when CP was combined with 8 ppm rapamycin. These results suggest that targeting two or more pathways achieve better treatment efficacy than a single-agent high-dose strategy that could increase the risk of side effects. A combination of CP and rapamycin may be a promising method of inhibiting muscle-invasive urothelial TCC.

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CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo

Cited by 21 publications

References 35 publications

Gold nanoparticles delivered miR-375 for treatment of hepatocellular carcinoma

Gold nanoparticles delivered miR-375 for treatment of hepatocellular carcinoma

Potential synergistic effects of sorafenib and CP‑31398 for treating anaplastic thyroid cancer with p53 mutations

Targeting mTOR and p53 Signaling Inhibits Muscle Invasive Bladder Cancer In Vivo

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