Napabucasin targets stemness markers, effectively killing stemness-high cancer cells from various tumors, except in prostate cancer (PCa). It inhibits PCa cell proliferation, motility, survival, and colony formation, while increasing apoptosis and sensitivity to docetaxel. Napabucasin also blocks sphere formation and kills prostate cancer stem cells (PrCSCs) and suppresses stemness gene expression. In PC-3 and 22RV1 cells, it reduces proliferation significantly from day 2 to 5 compared to controls (P<0.05) [1].
体内研究
Napabucasin (40 mg/kg) or Docetaxel significantly reduces tumor growth and volume in xenograft models, with Napabucasin showing even lower tumor volumes than Docetaxel in 22RV1 models (P<0.05). Both treatments also significantly reduce tumor weight compared to PBS (P<0.05) [1].
体外研究
Napabucasin targets stemness markers, effectively killing stemness-high cancer cells from various tumors, except in prostate cancer (PCa). It inhibits PCa cell proliferation, motility, survival, and colony formation, while increasing apoptosis and sensitivity to docetaxel. Napabucasin also blocks sphere formation and kills prostate cancer stem cells (PrCSCs) and suppresses stemness gene expression. In PC-3 and 22RV1 cells, it reduces proliferation significantly from day 2 to 5 compared to controls (P<0.05) [1].
Napabucasin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MiaPaCa2, AsPc1, Suit2, Panc1 cells
0.5 µM, 1.0 µM, 2.0 µM
2 hours
Measured STAT3 phosphorylation levels, found reduction in STAT3 phosphorylation after Napabucasin treatment
Clin Cancer Res. 2019 Dec 1;25(23):7162-7174.
Murine MDSC
1 µM
24 hours
Napabucasin significantly enhanced MDSC apoptosis and the expression of CD80 and MHC class II molecules, while slightly downregulating iNOS and Arg-1.
J Immunother Cancer. 2022 Mar;10(3):e004384.
CT26 cells
0.1, 0.5, 1, 2, 10 µM
24 hours
To evaluate the anti-tumor effect of NAP and N3-TMPs@NAP, results showed that the survival rate of cells in the N3-TMPs@NAP group decreased with increasing concentration.
J Nanobiotechnology. 2023 Feb 2;21(1):37.
DLD1 and HCT116 cells
2 µM
24 hours
BBI608 inhibited spherogenesis of DLD1 and HCT116 cell lines
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1839-44.
U87MG cells
1, 5, 10 µM
24, 48, 72 hours
Napabucasin significantly inhibited the proliferation of U87MG cells
J Exp Clin Cancer Res. 2019 Jul 5;38(1):289.
LN229 cells
1, 5, 10 µM
24, 48, 72 hours
Napabucasin significantly inhibited the proliferation of LN229 cells
J Exp Clin Cancer Res. 2019 Jul 5;38(1):289.
Hepa1–6 cells
5 µM
32 hours
Inhibition of IL-11-STAT3 signaling, reducing tumor cell proliferation
EBioMedicine. 2019 Aug;46:119-132.
Pancreatic cancer cell lines
0.01 – 5 µM
6 hours
Assessed cell viability, found differential sensitivity to Napabucasin across cell lines
Clin Cancer Res. 2019 Dec 1;25(23):7162-7174.
C57BL/6 mouse primary hepatocytes
0.1 mM
72 hours
To evaluate the effect of BBI608 on alcohol- and rmIL-6-induced Lcn2 mRNA expression, results showed that BBI608 pretreatment significantly suppressed Lcn2 mRNA expression.
Mol Ther. 2023 Sep 6;31(9):2662-2680.
CD44high FaDu cells
400 nM
72 hours
BBI608 inhibited spherogenesis of CD44high FaDu cells
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1839-44.
Human M-MDSC
0.5 µM
96 hours
Napabucasin completely abrogated the suppressive capacity of human M-MDSC on T-cell proliferation.
J Immunother Cancer. 2022 Mar;10(3):e004384.
CT26 cells
0.5 µM, 1 µM
To detect the protein and mRNA expression levels of CD44 and BMI1, results showed that the expression levels decreased with increasing NAP concentration.
J Nanobiotechnology. 2023 Feb 2;21(1):37.
Napabucasin 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
RET transgenic melanoma mouse model
Intraperitoneal injection
20 mg/kg
Twice a week for 4 weeks
Napabucasin significantly prolonged the survival of melanoma-bearing mice and promoted the accumulation of tumor-infiltrating antigen-presenting cells and activation of CD8+ and CD4+ T cells.
J Immunother Cancer. 2022 Mar;10(3):e004384.
Mice
Alcohol-induced liver metastasis model
Intraperitoneal injection
20 mg/kg
Every other day for 2 weeks
To evaluate the preventive effect of BBI608 on alcohol-induced liver metastasis, results showed that BBI608 pretreatment significantly suppressed alcohol-induced liver metastasis.
Mol Ther. 2023 Sep 6;31(9):2662-2680.
BALB/C mice
CT26 colon cancer model
Tail intravenous injection
20 mg/kg
14 days
To evaluate the anti-tumor effect of N3-TMPs@NAP, results showed that the tumor volume and weight in the N3-TMPs@NAP group were significantly lower than those in other groups.
J Nanobiotechnology. 2023 Feb 2;21(1):37.
Nude mice
Pancreatic cancer xenograft model
Intraperitoneal injection
20 mg/kg
Daily for 14 days
BBI608 significantly inhibited tumor growth in the pancreatic cancer xenograft model, and no tumor regrowth was observed during the posttreatment observation period
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1839-44.
Nude mice
Subcutaneous xenograft model of MiaPaCa2 Rosa26 or MiaPaCa2 NQO1–71 cells
Oral gavage
200 mg/kg
Once daily for 24 days
Evaluated the effect of Napabucasin on tumor growth, found that Napabucasin significantly inhibited the growth of MiaPaCa2 Rosa26 xenografts but had no significant effect on NQO1-knockout MiaPaCa2 xenografts
Clin Cancer Res. 2019 Dec 1;25(23):7162-7174.
Nude mice
Orthotopic glioma model
Intraperitoneal injection
40 mg/kg
Every other day, until the end of the experiment
Napabucasin significantly inhibited the growth of intracranial U87MG-derived tumors
J Exp Clin Cancer Res. 2019 Jul 5;38(1):289.
C57BL/6 mice
Hepatocellular carcinoma model
Intraperitoneal injection
40 mg/kg
Twice per week, for specified duration
Inhibition of STAT3 phosphorylation, reducing postoperative HCC recurrence
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