The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin on chemoresistant breast cancer cells

Abstract

BackgroundThe outcome of chemotherapy in breast cancer is strongly influenced by multidrug resistance (MDR). Several surrogate markers of chemoresistance have been identified including - CD24 (cluster differentiation 24) expression, stem cell growth factor (SCF), B-cell lymphocyte protein 2 (Bcl-2) and annexin V. The present study aimed to examine the expression of CD24 in the sensitive breast cancer cell line MCF-7 (Michigan Foudation-7) and MCF-7/adriamycin resistant (MCF-7/AdrRes) cells, and, if minimal effective doses of the anthracycline drug adriamycin (0.579 μM and 88.2 μM) would be enhanced by the antibody to SCF (anti-SCF).MethodsCD24 expression was analysed by flow cytometry. Both Bcl-2 and annexin V protein expression were quantitatively assessed by the enzyme-linked immunosorbent assay (ELISA).ResultsIn MCF-7/AdrRes cells the expression of CD24 was significantly higher compared to MCF-7 cells, 86.6% and 16.3% (p < 0.001), respectively. Bcl-2 expression was significantly increased in the presence of adriamycin and SCF (p < 0.038) and decreased in the presence of adriamycin and anti-SCF. When adriamycin, anti-SCF and SCF were combined or when adriamycin was used alone the decrease in Bcl-2 expression was insignificantly altered. In the presence of both adriamycin and SCF the expression of annexin V was decreased. However, it was significantly increased in the presence of adriamycin and anti-SCF (p < 0.042), as well as adriamycin, anti-SCF and SCF combined.In MCF-7 cells the effect of adriamycin alone or with either SCF, anti-SCF or anti-SCF or SCF combined, did not significantly alter the expression of Bcl-2. However, in the presence of both adriamycin and SCF the expression of annexin V was decreased, but was significantly increased in the presence of adriamycin and anti-SCF (p < 0.001), adriamycin, anti-SCF and SCF combined and adriamycin alone. Our results demonstrate that anti-SCF with low dose of adriamycin reduces Bcl-2 expression in MCF-7/AdrRes cells and increases annexin V expression in both MCF7/AdrRes and MCF-7 cells.ConclusionAdding anti-SCF to the chemotherapeutic regime of adriamycin may strongly enhance its chemotherapeutic effect in the treatment of patients with breast cancer.

MiR-139-5p reverses CD44+/CD133+-associated multidrug resistance by downregulating NOTCH1 in colorectal carcinoma cells

“…The presence of CSCs is one of the most important reasons for MDR [ 25 – 27 ]. As NOTCH1 promotes the maintenance of CSCs, we hypothesized that miR-139-5p reverses CD44+/CD133+-associated MDR by downregulating NOTCH1 .…”

Oct-4 is required for an antiapoptotic behavior of chemoresistant colorectal cancer cells enriched for cancer stem cells: Effects associated with STAT3/Survivin

“…Mechanisms of resistance to platinum agents such as oxaliplatin include enhanced DNA damage repair, decreased drug accumulation, detoxification and inactivation of platinum compounds [11,12]. Over the last few years there has been an increase in studies examining drug resistance mechanisms in malignant tumors through the establishment of drug resistant cell lines [13][14][15][16]. In vitro studies in several different CRC cell lines have shown that chronic exposure to oxaliplatin selects for a chemoresistant phenotype with the following properties: induction of epithelial-to-mesenchymal transition (EMT), which is important in tumor progression and metastasis [17]; enrichment for CSCs markers and the CSCs phenotype [13]; activation of multiple cell signaling pathways, such as the insulin-like growth factor-I receptor (IGF-IR) pathway, the epidermal growth factor receptor (EGFR) pathway [13,18] and cross-resistance (in addition to oxaliplatin resistance, cells become resistant to 5FU [13,19,20], and other agents, such as etoposide, and cisplatin [20]).…”

Anticancer activity of diterpenes and steroids from Eunicella singularis against two- and threedimensional breast cancer cell models

“…However, despite substantial research efforts, cancer therapy is still limited to classical radiotherapy and chemotherapy. Furthermore, current breast cancer treatments are also limited due to drug resistance and toxicity of drugs which indiscriminately kill both cancerous and normal cells [3][4][5]. Thus it is important to develop effective new anticancer compounds from natural sources with potent proapoptotic activity and weak side effects for breast cancer treatment and prevention.…”