Lenvatinib Exhibits Potent Anti-tumor Activity and Favorable Safety Profile in a Colorectal Cancer Xenograft Model.
Lenvatinib, a multikinase inhibitor, has shown potential anti-tumor activity in various cancers. This study evaluated its efficacy, safety, and apoptotic mechanisms in colorectal cancer (CRC) using HT-29 xenograft-bearing mice.
Mice were treated with lenvatinib at 0, 10, or 20 mg/kg for 20 days. Tumor growth, serum biochemistry, and histopathology were assessed. Protein expression related to ERK signaling and apoptosis was analyzed using immunohistochemistry.
Lenvatinib significantly suppressed CRC tumor growth, delaying progression up to 14-fold compared with controls. No body-weight loss or hepatic/renal toxicity was observed, indicating good tolerability. Mechanistically, lenvatinib reduced phosphorylated ERK and anti-apoptotic proteins (BCL-2, c-FLIP, XIAP) by 30-50%, while enhancing cleaved caspase-3, -8, -9, BAX, and BAK expression by 1.2-1.5-fold, promoting apoptosis.
Lenvatinib exhibits potent anti-CRC activity with minimal systemic toxicity. Its therapeutic effects are mediated through ERK pathway inactivation, suppression of anti-apoptotic proteins, and induction of caspase-dependent apoptosis.
Mice were treated with lenvatinib at 0, 10, or 20 mg/kg for 20 days. Tumor growth, serum biochemistry, and histopathology were assessed. Protein expression related to ERK signaling and apoptosis was analyzed using immunohistochemistry.
Lenvatinib significantly suppressed CRC tumor growth, delaying progression up to 14-fold compared with controls. No body-weight loss or hepatic/renal toxicity was observed, indicating good tolerability. Mechanistically, lenvatinib reduced phosphorylated ERK and anti-apoptotic proteins (BCL-2, c-FLIP, XIAP) by 30-50%, while enhancing cleaved caspase-3, -8, -9, BAX, and BAK expression by 1.2-1.5-fold, promoting apoptosis.
Lenvatinib exhibits potent anti-CRC activity with minimal systemic toxicity. Its therapeutic effects are mediated through ERK pathway inactivation, suppression of anti-apoptotic proteins, and induction of caspase-dependent apoptosis.