Improved antitumor activity of cisplatin combined with Ganoderma lucidum polysaccharides in U14 cervical carcinoma‐bearing mice

Abstract

Research on anticervical cancer is urgently required to enhance clinical outcomes. As a main anticancer drug for cervical carcinoma, cisplatin (CIS) has been used for a lot of years in clinical therapy. However, serious adverse effects including nephrotoxicity and neurotoxicity limit its long‐term treatment. Our main goal of this study is to investigate the improvement of Ganoderma lucidum polysaccharides (GPS) on CIS‐induced antitumor effect of in U14 cervical carcinoma‐bearing mice. The results showed that GPS + CIS could not only inhibit the growth of the tumor but also improve the spleen and thymus indexes. Moreover, little toxicological effects were observed on hepatic function and renal function in GPS + CIS treated mice bearing U14 tumor cells. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly, the expression of Bax increased and the expression of Bcl‐2 decreased dramatically in cervical cancer sections after oral administration of GPS + CIS for 14 days. This GPS/CIS combined therapy represents intriguing therapeutic strategy for U14 cervical carcinoma providing not only superior efficacy but also a higher safety level.

Herb–drug interactions between the medicinal mushrooms Lingzhi and Yunzhi and cytotoxic anticancer drugs: a systematic review

“…In-vitro Increase in tumor inhibition and apoptotic rate (dose-related or time-dependent) [98][99][100][101][102][103], similar effect at lower dose of 5-FU [105] Induce cell cycle arrest at different phases [99,101], increase caspase 3 and 8 expression and activity [100]. Increase release of cytochrome C [100,102] and MMP [102] Increase level of DNA strand breaks and oxidative damage in cancer cells [98] Enhance 5-FU cytotoxicity [118,119] Decrease dihydropyrimidine dehydrogenase mRNA expression, and increase IFN-α mRNA expression [118] Carboplatin Animal Less decrease in WBC [145] Increase in tumor inhibition and reduce death rate [68] Cisplatin Animal Prolong survival or increase survival rate [63][64][65][66], increase [64,66,104,125,174] or no effect [146,147,[175][176][177] on tumor inhibition, inhibit angiogenesis (decease microvessel density) [104] Influence on inflammatory cytokines (increase in interferons [146], TGF-β [127], increase or decrease in TNF-α [64,127,146,159], IL [64,…”

“…Retinoic acid Animal Reduce neural tube defects through up-regulating the transcription of CDK4 mRNA and expression of CDK4 and nestin at neural tube epithelia [186] No studies available Thioguanine Animal Prolong survival in additive function [63] No studies available UFT/Tegafur Animal No significant increase in efficacy [147] Reduce damage to intestine [173] and less reduction in WBC, but not platelet [147] Increase in cytotoxicity and inhibit metastasis [111] Reduce immunosuppression (phagocytic activity, antibody production) [111] Vincristine In-vitro Synergistic [110] or no significant effect [14] in tumor inhibition and reverse resistance [14] No studies available when co-administered with 5-FU, carboplatin, cisplatin, and doxorubicin which also shown benefits in clinical studies [63][64][65][66]. With regard to Yunzhi, the survival rate or time of animals increased when it was co-administered with 5-FU, cyclophosphamide, etoposide, and mitomycin, which were consistent with the findings from clinical studies [67][68][69][70][71][72][73][74].…”

“…Various invitro studies have shown that Lingzhi could enhance the tumor-inhibitory effect by reversing resistance to cytotoxic drugs [14][15][16] Lingzhi co-administration with cytotoxic drugs affects different pathways and cancer targets. In animal and invitro studies, various pathways related to cell cycle arrest, apoptosis, and angiogenesis were affected, including the Janus kinase/signal transducer and activator of transcription 3 (JAK-STAT3), the protein kinase B (Akt) [106,123] and the Human epidermal growth factor receptor 2 (HER2) signaling pathway [96,108], eventually affecting the apoptotic molecules, for example, by altering B-cell lymphoma (Bcl) and Bcl-2-associated X (Bax) [66,81,125], caspase 3 and 8 activation [81,100,107,125], and Fas and Fas Ligand (Fasl) [104]. The expression of other target genes or proteins was also affected, such as aquaporin [125,126], VEGF and basic fibroblast growth factor (bFGF) [104,127], and tumor metastasis suppressor gene 1 (TMSG-1) protein [91], all of which increased tumor inhibition.…”

Ganoderma Lucidum Polysaccharide, an Extract from Ganoderma Lucidum, Exerts Suppressive Effect on Cervical Cancer Cell Malignancy through Mitigating Epithelial-Mesenchymal and JAK/STAT5 Signaling Pathway

“…With development, it can cause vaginal bleeding, and even serious cases can cause ureteral obstruction [3], hydronephrosis, uremia, and malig-DOI: 10.1159/000505461 nant pericarditis [4]. At present, the main methods of treating the disease are radiotherapy, surgery, and chemotherapy [5]. However, many cases are diagnosed at the advanced stage, and the available treatments are often become ineffective at that time or even if they work, there exists a great possibility to recurrence [6].…”

“…Data from several studies suggested that GLP could play an anticancer role in colon cancer by inhibiting cell migration and promoting cell apoptosis [18]. Moreover, recent work by Zhu et al [5] has established that GLP could bind cisplatin to suppress the development of cervical cancer cells and improve the index of spleen and thymus. But the influences of GLP on the biological characteristics of cervical cancer cells and the signaling pathways involved in this process have not been elucidated.…”