ABSTRACT
MicroRNAs are a group of short non-coding RNAs (miRNAs), which are epigenetically involved in gene expression and other cellular biological processes and can be considered as potential biomarkers for cancer detection and support for treatment management. This review aims to amass the evidence in order to reach the molecular mechanism and clinical significance of miR-877 in different types of cancer. Dysregulation of miR-877 level in various types of malignancies as bladder cancer, cervical cancer, cholangiocarcinoma, colorectal cancer (CRC), gastric cancer, glioblastoma, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma, laryngeal squamous cell carcinoma, melanoma, non-small cell lung cancer (NSCLC), oral squamous cell carcinoma, ovarian cancer (OC), pancreatic ductal adenocarcinoma, and renal cell carcinoma (RCC) have reported, significantly increase or decrease in its level, which can be indicated to its function as oncogene or tumor suppressor. MiR-877 is involved in cell proliferation, migration, and invasion through cell cycle pathways in cancer. MiR-877 could be potential a candidate as a valuable biomarker for prognosis in various cancers. Through this study, we proposed that miR-877 can potentially be a candidate as a prognostic marker for early detection of tumor development, progression, as well as metastasis.
ABSTRACT
AIMS: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor. BACKGROUND: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment. OBJECTIVE: Evaluating anti-tumor activity of bortezomib liposomal formulations. METHODS: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models. RESULT: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice. CONCLUSION: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.
