Low-dose naltrexone plays antineoplastic role in cervical cancer progression through suppressing PI3K/AKT/mTOR pathway

Liu, Ning; Yan, Limei; Shan, Fengping; Wang, Xiaonai; Qu, Na; Handley, Mike; Ma, Mingxing

doi:10.1016/j.tranon.2021.101028

Cited by 14 publications

(7 citation statements)

References 28 publications

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“… Hela, Siha, C33A and Caski human cervical cancer cell lines were purchased from the Cell Bank of the Chinese Academy of Sciences ALB/C nude mice (4–6 weeks old) were purchased from Charles River (Beijing, China) LDN was dissolved in DMEM to 0.5, 1.5, 2, 3, and 5 mg/mL, and the culture was continued for 24, 48, and 72 h The mice were randomly divided into four groups with five animals in each group, including the control group, the 0.5 mg/kg group, the 5 mg/kg group, and the 10 mg/kg group based on the concentrations of LDN administered to the mice every day Suppressed the proliferation, migration and invasion abilities and promote apoptosis in Hela cells Inhibit cervical cancer progression in nude mice. Reduced the number of TAMs, mainly M2 macrophages, and decreased expression of anti-inflammatory factor IL-10 in the serum of nude mice Low-dose naltrexone plays antineoplastic role in cervical cancer progression through suppressing PI3K/AKT/mTOR pathway [ 47 ]. Human cervical cancer cell lines Hela and Siha (TCHu187 and TCHu113) were purchased from the Cell Bank of the Chinese Academy of Sciences 4 × 106 Hela cells (in 0.1 ml solution) were injected into BABL/c nude mice.…”

Section: Methodsmentioning

confidence: 99%

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Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

et al. 2022

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Purpose of Review Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action. Recent Findings We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Summary Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.

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Section: Methodsmentioning

confidence: 99%

“…The same authors postulate that low-dose NTX could upregulate the expression of OGFr. Furthermore, low-dose NTX indirectly reduced the expressions of phosphatidylinositol-3-kinase (PI3K/AKT), pAKT and mTOR in vitro and in vivo [ 47 ].…”

Section: Effect On Oncologic Outcomesmentioning

confidence: 99%

Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

et al. 2022

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“…Lycorine promoted apoptosis of gastric tumor cells by FBXW7-MCL1 axis [31]. Low-dose naltrexone inhibited PI3K/AKT/mTOR pathway and thus suppressed the proliferation of cervical cancer cells [32]. Tanespimycin acted as an antineoplastic drug through targeting HSP90 [33].…”

Section: Agingmentioning

confidence: 99%

Development and validation of an intra-tumor heterogeneity-related signature to predict prognosis of bladder cancer: a study based on single-cell RNA-seq

Zhou

Liang

Chen

et al. 2021

Aging

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Intra-tumor heterogeneity (ITH) was a potential mechanism of progression and drug resistance in bladder cancer (BCa). However, the understanding of ITH inBCa remains insufficient. Single-cell RNA sequencing (scRNA-seq) profiles of 2075 cells were analyzed, and 2940 cell markers were screened. The ITH of 396 cases was evaluated, and 96 ITH-related genes were identified. Based on the gene-pair strategy, 96 genes were cyclically paired, and an 8-gene-pair model was successfully established to evaluate the overall survival of BCa through Lasso and multivariate Cox regressions. The risk model showed high predictive value in the training dataset (n = 396, p = 0) and external validation datasets (n = 165, p = 2.497e-02; n = 224, p = 3.423e-02). The model was also valuable for the prediction of clinical treatment outcomes. Totally, a prognostic model based on scRNA-seq and ITH was successfully constructed and validated in large cohorts, providing novel clues for ITH study of BCa.

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“…The time of significant difference in mice treated with 0.5 mg/kg LDN was 34 days [74] LDN 0.5 mg/kg, LDN 5 mg/kg, LDN 10 mg/kg…”

Section: Ldn In In Vitro and In Vivo Experimental Modelsmentioning

confidence: 99%

“…Based on the results of the CCK-8 test, it was concluded that LDN can inhibit cancer cell proliferation in a time- and dose-dependent manner. The effect of LDN on the regulatory abilities of migration and invasion of the aforementioned cell lines was then examined, demonstrating that LDN treatment could significantly reduce the migration of Hela cells [ 74 ].…”

Section: Naltrexonementioning

confidence: 99%

Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy

Ciwun,

Tankiewicz-Kwedlo,

Pawlak

2024

Cancers

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Naltrexone (NTX) is a non-selective antagonist of opioid receptors, primarily used in the therapy of opioid and alcohol dependence. Low-dose naltrexone (LDN) exhibits antagonistic action against the opioid growth factor receptor (OGFr), whose signaling is associated with the survival, proliferation, and invasion of cancer cells. The mechanism of action of LDN depends on the dose and duration of the OGFr blockade, leading to a compensatory increase in the synthesis of the opioid growth factor (OGF), which has an inhibitory effect on carcinogenesis. Numerous studies on in vitro and in vivo models provide evidence of LDN’s positive impact on inhibiting the OGF–OGFr axis in cancers. LDN’s unique mechanism of action on cancer cells, lack of direct cytotoxic effect, and immunomodulating action form the basis for its use as an adjuvant in chemotherapy and immunotherapy of cancerous lesions.

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Low-dose naltrexone plays antineoplastic role in cervical cancer progression through suppressing PI3K/AKT/mTOR pathway

Abstract: Highlights LDN inhibited proliferation in cervical cancer. LDN inhibited migration and invasion in cervical cancer cells. LDN mediated the propagation property in cervical cancer through PI3K/AKT/mTOR signaling pathway.

Cited by 14 publications

References 28 publications

Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

Development and validation of an intra-tumor heterogeneity-related signature to predict prognosis of bladder cancer: a study based on single-cell RNA-seq

Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy

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