Expediting the development of robust 5-FU-resistant colorectal cancer models using innovative combined in vivo and in vitro strategies.

BACKGROUND: 5-Fluorouracil (5-FU) is a cornerstone in colorectal cancer therapy, but resistance has compromised its efficacy, necessitating detailed research into resistance mechanisms. Traditional methods for developing 5-FU-resistant cell lines are lengthy, unstable, and often unrepresentative of clinical scenarios. METHODS: We devised a rapid approach to create 5-FU-resistant colorectal cancer cells using an integrated in vivo/in vitro methodology. HCT116 cells were pretreated with 5-FU, then implanted into nude mice. Tumor growth was monitored, and cells from the tumors were cultured to establish the HCT116-Tumor cell line. Cells from 5-FU-exposed tumors received increasing 5-FU doses to induce resistance, creating the tumor-derived resistant (TR) cell line. Cells cultured without 5-FU were termed tumor-derived parental (TP) cells. An in vitro 5-FU resistance model, CR, served as a benchmark. Resistance metrics were evaluated using CCK-8 assays, Western Blotting, flow cytometry, and in vivo studies. Proteomics identified resistance-related differentially expressed proteins (DEPs). RESULTS: Low-dose 5-FU pretreatment accelerated tumor growth. Combining in vivo and in vitro methods, we developed 5-FU-resistant TR cells within two and a half months, faster than the ten-month conventional protocol. TR cells showed stronger and more durable 5-FU resistance than CR cells, with inhibited apoptosis, autophagy, and ferroptosis, and activation of MDR1. Proteomic analysis indicated more DEPs in TR cells, suggesting unique resistance mechanisms. Animal studies confirmed enhanced drug resistance in TR cells. CONCLUSIONS: Our integrated approach rapidly develops colorectal cancer cells with robust 5-FU resistance, offering a potent model for exploring multiple resistance pathways and counter-resistance strategies.

Exosomes: Key Factors in Ovarian Cancer Peritoneal Metastasis and Drug Resistance.

Ovarian cancer remains a leading cause of death among gynecological cancers, largely due to its propensity for peritoneal metastasis and the development of drug resistance. This review concentrates on the molecular underpinnings of these two critical challenges. We delve into the role of exosomes, the nano-sized vesicles integral to cellular communication, in orchestrating the complex interactions within the tumor microenvironment that facilitate metastatic spread and thwart therapeutic efforts. Specifically, we explore how exosomes drive peritoneal metastasis by promoting epithelial-mesenchymal transition in peritoneal mesothelial cells, altering the extracellular matrix, and supporting angiogenesis, which collectively enable the dissemination of cancer cells across the peritoneal cavity. Furthermore, we dissect the mechanisms by which exosomes contribute to the emergence of drug resistance, including the sequestration and expulsion of chemotherapeutic agents, the horizontal transfer of drug resistance genes, and the modulation of critical DNA repair and apoptotic pathways. By shedding light on these exosome-mediated processes, we underscore the potential of exosomal pathways as novel therapeutic targets, offering hope for more effective interventions against ovarian cancer's relentless progression.

LncRNA PART1 promotes malignant biological behaviours associated with head and neck cancer cells via synergistic action with FUT6.

The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.