SCF is abundantly expressed in a broad spectrum of human malignancies, such asSCLC, NSCLC, colon, breast and renal cancers, acting through both activation of its receptor KIT and paracrine angiogenesis factor. Lenvatinib is a multiple receptor tyrosine kinases inhibitor with IC50 values of 4.0nM, 5.2nM, 22nM, 39nM, 46nM, 51nM and 100nM for VEGFR2, VEGFR3, VEGFR1, PDGFRβ, FGFR1, PDGFRα and Kit (measured by HTRF assays), respectively. Exposure to Lenvatinib inhibited SCF-induced KIT (Tyr719) phosphorylation and VEGF-induced KDR (Tyr996) phosphorylation in HUVEC with IC50 values of 1.9nM and 0.83nM. Consistent with its inhibition of this two targets, the sandwich tube formation (sTF) assay showed that treatment with Lenvatinib inhibited either VEGF or SCF-induced tube formation of HUVEC in a dose-dependent manner with IC50s of 5.2 and 5.1nM, respectively. Though Lenvatinib did not show the potent inhibitory activities against H146 cells expressing SCF, but not KIT, it inhibited SCF-induced cell proliferation of human SCLC, H526 cells expressing KIT, suggesting the inhibition by Lenvatinib on cell growth through paracrine. Oral administration of Lenvatinib at dose of 30 and 100 mg/kg (BID, QDx21) caused tumor growth in a dose-dependent manner in H146 xenograft, while tumor regression achieved at dose of 100mg/kg with decreased microvessel density[1].
Lenvatinib/仑伐替尼 细胞实验
Cell Line
Concentration
Treated Time
Description
References
TPC-1
15 nM
Establish lenvatinib-resistant cell lines and analyze resistance mechanisms
Cancer Sci. 2022 Sep;113(9):3193-3210.
FRO
30 nM
Establish lenvatinib-resistant cell lines and analyze resistance mechanisms
Cancer Sci. 2022 Sep;113(9):3193-3210.
SMMC-7721
10 μM
24 h
To evaluate the effect of Lenvatinib on STOML2 expression, it was found that Lenvatinib significantly upregulated STOML2 expression
J Hematol Oncol. 2021 Jan 14;14(1):16.
HCCLM3
10 μM
24 h
To evaluate the effect of Lenvatinib on STOML2 expression, it was found that Lenvatinib significantly upregulated STOML2 expression
J Hematol Oncol. 2021 Jan 14;14(1):16.
HepG2 cells
80 µM
14 days
To identify key genes associated with Lenvatinib resistance, it was found that DUSP4 deficiency enhanced Lenvatinib resistance and maintained cell proliferation, survival, and migration ability.
Int J Biol Sci. 2022 Jul 4;18(11):4357-4371.
Huh7 cells
20 µM
24 h
To validate the role of DUSP4 in Lenvatinib resistance, it was found that DUSP4 deficiency enhanced Lenvatinib resistance and maintained cell proliferation, survival, and migration ability.
Int J Biol Sci. 2022 Jul 4;18(11):4357-4371.
Hep3B cells
10 μM
48 h
To evaluate the effect of Lenvatinib on apoptosis in Hep3B cells, results showed that Lenvatinib induced apoptosis.
Cell Death Dis. 2022 Mar 2;13(3):200.
Hep3B/CSQT-2 cells
2.5 μM
7 days
To evaluate the effect of Lenvatinib on colony growth in Hep3B/CSQT-2 cells, results showed that Lenvatinib inhibited colony growth.
Cell Death Dis. 2022 Mar 2;13(3):200.
Caki-1 cells
20 µM
72 h
To study the effect of Lenvatinib on the viability of renal cancer cells, results showed that Lenvatinib significantly decreased the viability of renal cancer cells
Cells. 2022 Apr 25;11(9):1448.
786-O cells
20 µM
72 h
To study the effect of Lenvatinib on the viability of renal cancer cells, results showed that Lenvatinib significantly decreased the viability of renal cancer cells
Cells. 2022 Apr 25;11(9):1448.
A-498 cells
20 µM
72 h
To study the effect of Lenvatinib on the viability of renal cancer cells, results showed that Lenvatinib significantly decreased the viability of renal cancer cells
Cells. 2022 Apr 25;11(9):1448.
HepG2 cells
20 or 40 μM
48 h
To evaluate the cytotoxicity of Lenvatinib on HepG2 cells, the results showed that 20 μM of Lenvatinib had a limited role in inducing apoptosis.
J Adv Res. 2023 Feb;44:173-183.
Huh7 cells
20 or 40 μM
48 h
To evaluate the cytotoxicity of Lenvatinib on Huh7 cells, the results showed that both 20 and 40 μM of Lenvatinib significantly induced apoptosis.
J Adv Res. 2023 Feb;44:173-183.
PLC/PRF5 cells
20 or 40 μM
48 h
To evaluate the cytotoxicity of Lenvatinib on PLC/PRF5 cells, the results showed that 20 μM of Lenvatinib had a limited role in inducing apoptosis.
J Adv Res. 2023 Feb;44:173-183.
Hep3B cells
20 or 40 μM
48 h
To evaluate the cytotoxicity of Lenvatinib on Hep3B cells, the results showed that both 20 and 40 μM of Lenvatinib significantly induced apoptosis.
J Adv Res. 2023 Feb;44:173-183.
HCCLM3
0.00001, 0.0001, 0.001, 0.01, 1, 10 and 100 μM
72 h
To evaluate the sensitivity of HCC cells to Lenvatinib, the results showed that HCC cells with high TBC1D31 expression significantly increased resistance to Lenvatinib.
Adv Sci (Weinh). 2024 Oct;11(40):e2405459.
HepG2
0.00001, 0.0001, 0.001, 0.01, 1, 10 and 100 μM
72 h
To evaluate the sensitivity of HCC cells to Lenvatinib, the results showed that HCC cells with high TBC1D31 expression significantly increased resistance to Lenvatinib.
Adv Sci (Weinh). 2024 Oct;11(40):e2405459.
Lenvatinib/仑伐替尼 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c-nu nude mice
TPC-1/LR tumor xenograft model
Oral
6 mg/kg
Once daily for 9 days
Evaluate the antitumor effect of lenvatinib and lapatinib combination on TPC-1/LR tumors
Cancer Sci. 2022 Sep;113(9):3193-3210.
Mice
8505 C cell xenograft model
Oral
25 mg/kg
Once daily for 3 weeks
To evaluate the efficacy of Lenvatinib in combination with BRAF inhibitor PLX4720 for the treatment of BRAF-mutant thyroid cancer. The results showed that Lenvatinib monotherapy significantly suppressed tumor growth, and the inhibitory effect of PLX4720 was further enhanced when combined with Lenvatinib.
Cell Mol Life Sci. 2024 May 25;81(1):238.
Nude mice
HCCLM3 xenograft model
Intraperitoneal injection
5 mg/kg or 10 mg/kg
Daily until the end of the experiment
To evaluate the inhibitory effect of Lenvatinib on HCC growth, it was found that Lenvatinib significantly suppressed tumor growth, and the combination with hydroxychloroquine was more effective
J Hematol Oncol. 2021 Jan 14;14(1):16.
BALB/C nude mice
Xenograft tumor model
Oral gavage
30 mg/kg/d
Daily for 4 weeks
To evaluate the effect of DUSP4 deficiency on Lenvatinib resistance, it was found that DUSP4 deficiency impaired the anti-tumor effects of Lenvatinib and enhanced tumor growth.
Int J Biol Sci. 2022 Jul 4;18(11):4357-4371.
Mice
Hepa1-6 hepatoma orthotopic model
Oral
10 mg/kg
Once daily for two weeks
To evaluate the anti-angiogenic effects of Lenvatinib on tumor angiogenesis, the results showed that Lenvatinib significantly inhibited tumor angiogenesis.
iScience. 2024 Jan 4;27(2):108797
Nude mice
PDX model
Intraperitoneal injection
60 mg/kg
Daily for 24 days
To evaluate the effect of Lenvatinib on tumor growth in PDX model, results showed that Lenvatinib significantly inhibited tumor growth.
Cell Death Dis. 2022 Mar 2;13(3):200.
BALB/c nude mice
Huh7 cell xenograft model
Intragastric administration
10 or 30 mg/kg
Once daily for two weeks
To evaluate the anti-tumor effect of Lenvatinib in vivo on the Huh7 cell xenograft model, the results showed that both 10 and 30 mg/kg/d of Lenvatinib significantly inhibited tumor growth.
J Adv Res. 2023 Feb;44:173-183.
Nude mice
HCC cell line-derived xenograft model
Oral
4 mg/kg
Every 5 days until tumor volume reaches 1500 mm³
To evaluate the effect of TBC1D31 knockdown on the anti-tumor efficacy of Lenvatinib, the results showed that TBC1D31 knockdown significantly increased the sensitivity of HCCLM3 cells to Lenvatinib.
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