Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Abstract

Background As an immune enhancer, Nocardia rubra cell‐wall skeleton (Nr‐CWS) has been used to treat persistent human papillomavirus infection and cervical precancerous lesions. However, it is still unclear whether it can be used to treat cervical carcinoma. Methods In our study, the aim was to determine whether Nr‐CWS affects the apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages in vivo and in vitro. Results The experimental results showed that Nr‐CWS can promote the activity of dendritic cells and macrophages and reduce their apoptosis. It also increased the cytokines IL‐6, IL‐12, TNF‐ɑ, and IL‐1β secreted by dendritic cells and macrophages and reduced their PD‐L1 expression. In vitro, Nr‐CWS inhibited the proliferation, colony forming ability of HeLa and SiHa cervical carcinoma cell lines cultured with macrophages, and more cells were blocked in G2/M phase. Nr‐CWS promoted TNF‐ɑ/TNFR1/caspase‐8‐mediated apoptosis by increasing macrophages secretion of TNF‐ɑ and inhibited cell migration and invasion regulated by the WNT/β‐catenin‐EMT pathway. Nr‐CWS also reduced the expression of the cervical carcinoma genes E6 and E7 thereby increasing expression of p53 gene and decreasing expression of PD‐L1 gene. In vivo, Nr‐CWS inhibited tumor growth and decreased the expression of E6, E7, PD‐L1, P16, Ki67, and PCNA in tumors. Conclusions Therefore, our results suggest that Nr‐CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages.

Nocardia rubra cell-wall skeleton activates an immune response in cervical tissue via stimulating FPR3 to enhance dendritic cell-mediated Th1 differentiation

“…Maturation of DCs can be promoted by bacterial components, inflammatory cytokines, or antigen-antibody complexes (36). Nr-CWS is a bacterial-derived extract that activates DCs in vitro (20). In the present study, Nr-CWS enhanced HLA-DR, CD86, and CD83 expression in DCs, increased IL-12 production, and reduced IL-10 production.…”

“…Recently, it has been proposed that Nr-CWS facilitates the proliferation and viability of DCs (19). Zhang et al reported that Nr-CWS can promote the maturation of DCs (20). Based on these findings, we explored the response of T cells to DCs stimulated by Nr-CWS.…”

The effect of aminolevulinic acid hydrochloride topical powder photodynamic therapy versus nocardia rubra cell wall skeleton and observers group in the treatment of cervical low-grade squamous intraepithelial lesions with human papillomavirus infection: A non-randomized study, controlled pilot study

“…[25] A study suggests that Nr CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages. [9] In order to evaluate the effectiveness of 5-ALA PDT for the treatment of cervical LSIL paired with HPV, our study used Nr-CWS as the control group. At 4 to 6 or 12 months of follow-up, our study observed no statistically significant difference in HPV remission between the Nr-CWS group and the 5-ALA PDT group.…”

“…[8] Nocardia rubra cell-wall skeleton (Nr-CWS), an immune booster, has been utilized to treat cervical precancerous lesions and persistent HPV infection. [9] A brand-new, minimally invasive treatment method is called photodynamic therapy (PDT). [10] PDT has been recommended as a preferred method for genital warts, skin basal cell carcinoma, and other diseases, but its availability in treating cervical squamous intraepithelial lesion is still unidentified.…”

The Nocardia Rubra Cell Wall Skeleton Regulates Macrophages and Promotes Wound Healing

“…The Nocardia rubra cell wall skeleton (Nr-CWS) was extracted from a rubra, a gram-positive bacterium that consists of nocardia acid, arabinogalactan, and mucopolysaccharide. Previous studies have shown that Nr-CWSs can act as an immunomodulator to upregulate the body’s immune function for antitumor purposes, and it can also accelerate the wound repair process in patients with celiac disease [ 1 ]. Some researchers have applied it to mouse skin wounds and found that it can promote healing [ 2 ].…”