Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer

Chen, Yiqing; Zhu, Wenting; Lin, Cai-Yan; Yuan, Zhongwen; Li, Zhenhua; Yan, Pengke

doi:10.2147/ijn.s270939

Cited by 24 publications

(11 citation statements)

References 44 publications

(52 reference statements)

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“…ZCL278 has become a selective Cdc42 small molecule regulator, which directly binds to Cdc42 and inhibits its function (53). Rapamycin is a specific inhibitor of mTOR protein, which binds to intracellular receptor FKBP-12 to form a complex and then directly acts on the FRB domain of mTOR to inhibit protein activity (54). In the past few years, Rapamycin has been developed as a treatment for a variety of cancers.…”

Section: Discussionmentioning

confidence: 99%

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

Song

et al. 2021

Front. Oncol.

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Autophagy and apoptosis are dynamic processes that determine the fate of cells, and regulating these processes can treat cancer. GEFT is highly expressed in rhabdomyosarcoma (RMS), which accelerates the tumorigenicity and metastasis of RMS by activating Rac1/Cdc42 signaling, but the regulatory mechanisms of autophagy and apoptosis are unclear. In our study, we found that the RMS tissues had high Rac1, Cdc42, mTOR, and Bcl-2 expression levels and low Beclin1, LC3, and Bax expression levels compared with the normal striated muscle tissues (P < 0.05). In addition, multivariate analysis has proven that Rac1 is an independent prognostic factor (P < 0.05), and the high expression level of the Beclin1 protein was closely associated with the tumor diameter of the RMS patients (P = 0.044), whereas the high expression level of the LC3 protein was associated with the clinical stage of the RMS patients (P = 0.027). Furthermore, GEFT overexpression could inhibit autophagy and apoptosis in RMS. A Rac1/Cdc42 inhibitor was added, and the inhibition of autophagy and apoptosis decreased. Rac1 and Cdc42 could regulate mTOR to inhibit autophagy and apoptosis in RMS. Overall, these studies demonstrated that the GEFT–Rac1/Cdc42–mTOR pathway can inhibit autophagy and apoptosis in RMS and provide evidence for innovative treatments.

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Section: Discussionmentioning

confidence: 99%

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

Song

et al. 2021

Front. Oncol.

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“…Mice were treated with Rapa/Lps through tail vein injection twice a week, and 5-FU through intraperitoneal injection twice a week. The duration for Rapa/Lps and 5-FU administration was specified by Chen et al 11 and Khondee et al 14 , We monitored the weight twice a week for a month during the experiment.…”

Section: Methodsmentioning

confidence: 99%

“… 10 Our previous study developed a rapamycin liposomes system (abbreviated to, Rapa/Lps) to address this problem, and we discovered that Rapa/Lps effectively suppressed the tumor growth in the HCT-116 xenograft model. 11 However, xenograft models were limited by the lack of broad molecular transformations like human tumors, and their growth rates were considerably faster than primary tumors. 12 As a result, the xenograft was unable to provide a clear indication of the potential effects of rapamycin liposomes with 5-FU.…”

Section: Introductionmentioning

confidence: 99%

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

Liu¹,

Zhu²,

Jia³

et al. 2022

IJN

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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.

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“…The cytotoxic potential of the folate-liposomal 5-FU was superior for all screened tumor cell lines in comparison with free 5-FU and 5-FU non-functionalized liposomes and was minimal on normal cells, while in vivo experiments revealed an augmented decrease of the tumor volume after exposure to 5-FU folate liposomes vs. free 5-FU. Chen and colleagues [148] designed another strategy for improving 5-FU treatment efficacy in CRC by developing, through the ethanol injection method, rapamycin loaded liposomes that can be administrated either alone due to the anticancer activity [154,155] of rapamycin or assist the free 5-FU treatment to potentate its cytotoxic activity. The obtained results showed that the cellular uptake, cytotoxic, and apoptotic potential were enhanced following liposomal encapsulation of free rapamycin.…”

Section: Lipid-based Drug-delivery Systemsmentioning

confidence: 99%

“…Chen and colleagues [ 148 ] designed another strategy for improving 5-FU treatment efficacy in CRC by developing, through the ethanol injection method, rapamycin loaded liposomes that can be administrated either alone due to the anticancer activity [ 154 , 155 ] of rapamycin or assist the free 5-FU treatment to potentate its cytotoxic activity. The obtained results showed that the cellular uptake, cytotoxic, and apoptotic potential were enhanced following liposomal encapsulation of free rapamycin.…”

Section: Organic Nanosized Drug-delivery Systems For Crc Therapymentioning

confidence: 99%

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients

et al. 2021

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Globally, colorectal cancer (CRC) ranks as one of the most prevalent types of cancers at the moment, being the second cause of cancer-related deaths. The CRC chemotherapy backbone is represented by 5-fluorouracil, oxaliplatin, irinotecan, and their combinations, but their administration presents several serious disadvantages, such as poor bioavailability, lack of tumor specificity, and susceptibility to multidrug resistance. To address these limitations, nanomedicine has arisen as a powerful tool to improve current chemotherapy since nanosized carriers hold great promise in improving the stability and solubility of the drug payload and enhancing the active concentration of the drug that reaches the tumor tissue, increasing, therefore, the safety and efficacy of the treatment. In this context, the present review offers an overview of the most recent advances in the development of nanosized drug-delivery systems as smart therapeutic tools in CRC management and highlights the emerging need for improving the existing in vitro cancer models to reduce animal testing and increase the success of nanomedicine in clinical trials.

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Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer

Cited by 24 publications

References 44 publications

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

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

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients

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