The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: The role of OGFr, BCL2, and immune response

Abstract

AimsCancer is a major worldwide health problem. Cancer cells express opioid growth factor (OGF) which controls their growth. Naltrexone in low dose (LDN) blocks opioid receptors intermittently and controls the replication of cancer cells. The aim of this study was to investigate the effect of LDN and its chemotherapeutic additive effect on the growth of solid Ehrlich carcinoma in mice with focus on the OGFr and immune responses. Main methodsSixty female Swiss albino mice were assigned into 5 groups (n: 12 mice each): (i): normal control, (ii): Solid Ehrlich carcinoma (SEC), (iii): SEC treated with LDN, (iv): SEC treated with 5-fluorouracil (5-FU), (v): SEC treated with LDN + 5-FU. All drugs were started when the tumor became palpable on 9th day. At the end of the study animals were sacrificed, blood and tissue samples were collected. Tumor weight and volume were measured. Splenocytes and myeloid derived suppressor cells (MDSC) were counted. Tumor expression of opioid growth factor receptors (OGFr), serum level of IFN-γ, tumor histopathology (H&E) and immunohistochemistry staining of p21, p53, Bcl2 were assessed. Key findingsAll drug-treated groups showed reduction in tumor weight and volume, significant increase of splenocyte with tendency to reduce MDSC cell counts. LDN led to significant increase in OGFr both in solo and in combination with 5FU. Serum IFN-γ is significantly increased by LDN but decreased by 5-FU. Also, LDN and 5FU increased immunehistochemical staining of p21 while decreased immunostaining of Bcl2. In animals treated with a combination of LDN and 5FU a maximal downregulation of the antiapoptotic mediator BCL2 was observed. SignificanceThe current study suggested that LDN may play a role in inhibiting cancer cell growth and highlights the possibility of promising combination with cancer chemotherapeutics, which guarantee further clinical studies for approval.