Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC (Min/+) Mice and AOM/DSS-Induced Colorectal Cancer Mice

Abstract

Background Transgenic C57BL/6-APC (Min/+) spontaneous cancer mouse model and the Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) chemically induced orthotopic colorectal cancer mouse model represented distinct pathogenesis of colorectal cancers. Our previous study revealed that the combination of Rapamycin liposomes (Rapa/Lps) and 5-Fluorouracil (5-FU) has anti-colorectal cancer effects. However, the therapeutic efficacy of Rapa/Lps and 5-FU in other colorectal cancer mice models is yet to be thoroughly explored. The purpose of this study was to investigate the anti-tumor effect of Rapa/Lps combined with 5-FU in vivo and in vitro. Methods In this study, we evaluated the effect of Rapa/Lps and 5-FU on APC (Min/+) mice and AOM/DSS-induced colorectal cancer mice. The small intestine, colorectum, serum, and plasma of mice in each group were collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to intestine tissues. Tube formation assay, Transwell assay, wound healing assay, Western Blot were used to explore the anti-angiogenesis effect of drugs in HUVECs. Results As expected, Rapa/Lps and 5-FU significantly suppressed tumor formation, decreased the number of tumors, and tumor load both in two mouse models, and had no influence on mouse weight. Mechanically, the anti-tumor effect of the drug also was associated in inhibiting angiogenesis and proliferation. Furthermore, we found that Rapa/Lps obviously inhibited HUVECs tube formation and migration. Conclusion Altogether, we revealed the Rapa/Lps synergism with 5-FU decreased colon and small intestinal tumorigenesis in AOM/DSS-treated and APC (Min/+) mice, respectively, and correlated with anti-angiogenesis.

MAPKAP1 orchestrates macrophage polarization and lipid metabolism in fatty liver-enhanced colorectal cancer

“…Subsequently, we replicated this cycle thrice to induce colorectal cancer (CRC) in mouse models [25] . Finally, the mice were euthanized by cervical dislocation using isoflurane (R510–22–10, RWD Life Science, Shenzhen, China).…”

Multifunctional and stimuli-responsive liposomes in hepatocellular carcinoma diagnosis and therapy

“…Moreover, treatment of skin cancer with phototherapy effect of liposomal nanocarriers can be facilitated [57] . According to the studies, it is highly suggested to use liposomes for purpose of cancer therapy and chemotherapy due to their high potential [58] , [59] , [60] , [61] and in next section, use of liposomes for HCC treatment is discussed ( Fig. 1 ).…”

Experimental Murine Models for Colorectal Cancer Research

“…The histological analysis of Apc mutation-induced tumors of the colon revealed that they are benign adenomas, making this model appropriate for investigating the premalignant rather than malignant phases of CRC. Nevertheless, tumor malignancy increases, and latency time shortens when AOM or other carcinogenic compound is administered [117,119,120]. Despite the fact that additional Apc-targeting murine models have been developed (Apc ∆716 , Apc ∆14 , Apc 1638N , among others), Apc Min/+ continues to be the most widely employed transgenic murine model of CRC [43].…”