维替泊芬激活TAp73并抑制硫氧还蛋白还原酶以改善突变型胰腺肿瘤的癌症治疗效果。
Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy in mutant pancreatic tumors.
作者信息
Acedo Pilar, Fernandes Aristi, Zawacka-Pankau Joanna
机构信息
Department of Microbiology, Tumor & Cell Biology, Karolinska Institutet, Biomedicum, Solnavägen 9, 171 65, Stockholm, Sweden.
Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Biomedicum, Solnavägen 9, 171 65, Stockholm, Sweden.
出版信息
Future Sci OA. 2019 Jan 18;5(2):FSO366. doi: 10.4155/fsoa-2018-0082. eCollection 2019 Feb.
AIM
TAp73 is a tumor suppressor, which compensates for p53 loss and induces apoptosis in tumors in response to genotoxic stress or small-molecule treatments. Pancreatic ductal adenocarcinoma has a late onset of the disease, responds poorly to the existing therapies and has a very low survival rates.
RESULT
Here, using drug-repurposing approach, we found that protoporphyrin IX (PpIX) and benzoporphyrin derivative (BPD) monoacid ring A activate TAp73 and induce apoptosis in pancreatic cancer cells. PpIX and BPD induce reactive oxygen species and inhibit thioredoxin reductase 1.
CONCLUSION
Thus, PpIX and BPD target cancer cells' vulnerabilities namely activate TAp73 tumor suppressor and inhibit oncogenic Trx1. Our findings may contribute to faster repurposing of PpIX and BPD to treat pancreatic tumors.
目的
TAp73是一种肿瘤抑制因子，可弥补p53缺失，并在肿瘤细胞因基因毒性应激或小分子治疗而产生反应时诱导细胞凋亡。胰腺导管腺癌发病较晚，对现有治疗反应不佳，生存率极低。
结果
在此，我们采用药物重新利用方法，发现原卟啉IX（PpIX）和苯并卟啉衍生物（BPD）单酸环A可激活TAp73并诱导胰腺癌细胞凋亡。PpIX和BPD可诱导活性氧生成并抑制硫氧还蛋白还原酶1。
结论
因此，PpIX和BPD针对癌细胞的脆弱点，即激活TAp73肿瘤抑制因子并抑制致癌性Trx1。我们的研究结果可能有助于更快地将PpIX和BPD重新用于治疗胰腺肿瘤。
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