Abstract
BackgroundChemotherapy is a primary approach in cancer treatment after routine surgery. However, chemo-resistance tends to occur with chemotherapy in clinic, resulting in poor prognosis and recurrence. Nowadays, Chinese medicine may shed light on design of new therapeutic modes to overcome chemo-resistance. Although Rhizoma Curcumae possesses anti-cancer activities in various types of cancers, the effects and underlying mechanisms of its bioactive components against chemo-resistance are not clear. Therefore, the present study aims to explore the potential effects of Rhizoma Curcumae on doxorubicin-resistant breast cancer cells.MethodsThe expression and function of ABC transporters in doxorubicin-resistant MCF-7 breast cancer cells were measured by western blotting and flow cytometry. Cell viability was detected using MTT assay. The combination index was analyzed using the CalcuSyn program (Biosoft, Ferguson, MO), based on the Chou–Talalay method.ResultsIn our present study, P-gp was overexpressed at protein level in doxorubicin-resistant MCF-7 cell line, but short of MRP1 and BCRP1. Essential oil of Rhizoma Curcumae and the main bioactive components were assessed on doxorubicin-resistant MCF-7 cell line. We found that the essential oil and furanodiene both display powerful inhibitory effects on cell viability, but neither of these is the specific inhibitor of ABC transporters. Moreover, furanodiene fails to enhance the efficacy of doxorubicin to improve multidrug resistance.ConclusionOverall, our findings fill the gaps of the researches on chemo-resistance improvement of Rhizoma Curcumae and are also beneficial for Rhizoma Curcumae being developed as a promising natural product for cancer adjuvant therapy in the future.
Highlights
Chemotherapy is a primary approach in cancer treatment after routine surgery
Establishment and characterization of doxorubicin‐resistant MCF‐7 breast cancer cell line Doxorubicin-resistant MCF-7 breast cancer cell line was established by a stepwise exposure of MCF-7 cells to increasing concentrations of doxorubicin
Our results show that doxorubicin-resistant MCF-7 cells are resistant to doxorubicin with an IC50 value of 73.45 μM
Summary
Chemotherapy is a primary approach in cancer treatment after routine surgery. chemoresistance tends to occur with chemotherapy in clinic, resulting in poor prognosis and recurrence. Chemotherapy is regarded as one of adjuvant therapy after a routine surgery and being the primary approach for various cancer types [1,2,3]. Many obstacles, including low efficacy and side effects, especially for chemo-resistance, still exist in cancer patients undergoing chemotherapy. There are a lot of strategies overcoming chemo-resistance, such as targeting ATP-binding cassette (ABC) transporters [4, 5], inducing cell apoptosis [6], inhibiting DNA repair [7], regulating metabolic reprogramming [8, 9], or applying combination therapy [10]. The role of ABC transporters is found to be closely related with chemo-resistance, thereby leading to poor prognosis and tumor recurrence in clinic [11]. A thorough mechanisms of ABC transporters in chemo-resistance are still ongoing, and some typical proteins have been hot topics for a long time, including P-glycoprotein 1 (P-gp, MDR1, or ABCB1) [13], multidrug resistance-associated protein 1 (MRP1) [14], and ATP-binding cassette sub-family G member 2 (ABCG2 or BCRP) [15, 16]
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