Quercetin/curcumin suppresses pancreatic tumor growth and enhances chemosensitivity in a Capan-1 xenograft model.

backgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, with a five-year survival rate of only 6%. Its aggressive biology, early metastasis, and remarkable resistance to chemotherapy and radiation contribute to poor outcomes. Novel treatment strategies are urgently needed. Quercetin(Q) and curcumin(C) are plant-derived polyphenols known for anti-cancer properties, low toxicity, and potential to overcome drug resistance. This study evaluates the therapeutic efficacy of quercetin/curcumin (Q/C) in an in vivo PDAC model using Capan-1 (a chemoresistant human PDAC cell line) xenografts in nude mice, alone and in combination with cisplatin.

methodsThirty-four nude mice with established subcutaneous Capan-1 tumors were randomized into six groups (n = 7 each): Control, cisplatin only, Q/C (oral), Q/C (intraperitoneal, IP), cisplatin + Q/C(in drinking water), and a prophylactic Q/C group (Q/C given 5 days prior to tumor inoculation). Q/C (quercetin–curcumin solution) was administered daily by oral gavage, IP injection, or ad libitum in water for 28 days. Cisplatin (20 mg/kg IP) was given for 5 consecutive days at the start of treatment and repeated 3 weeks later. Tumor size was measured periodically, and at the endpoint, the excised tumors were weighed and processed for histopathological examination (H&E staining). Tumor dimensions and volumes were recorded, and the fraction of necrotic tumor area was quantified by microscopic image analysis.

resultsQ/C treatment is described with a mean difference and 95% CI (no p-value), inhibiting tumor growth in vivo. At matched time points, mice receiving Q/C monotherapy (oral or i.p.) exhibited ~ 40% lower in-life tumor volumes than untreated controls, with an effect similar in magnitude to cisplatin monotherapy (~ 40% mean reduction; longitudinal descriptive analysis with 95% CIs; final tumor-weight differences evaluated separately by one-way ANOVA with Tukey HSD). The combination of cisplatin + Q/C produced the greatest suppression of tumor growth, with final tumor weight (3.16 g) reduced by 72% relative to control (11.3 g) and described with a mean difference and 95% CI (no p-value), smaller tumor dimensions (approx. 2.3 × 1.9 × 1.2 cm vs. 3.9 × 2.5 × 2.2 cm in control). Tumor growth curves showed a substantially slower increase in volume with Q/C, especially when combined with cisplatin, compared to the rapid growth observed in the control and cisplatin-only groups. Prophylactic quality control (Q/C) administered prior to tumor implantation was not associated with a measurable delay in tumor development; time-to-onset estimates closely overlapped those of the controls, and point estimates with 95% confidence intervals were compatible with no material effect. Histopathological analysis revealed increased tumor necrosis in all treated groups. The mean necrotic area in tumors was 57–67% in the oral and IP Q/C groups and 47.5% in the combination group, compared to only 32.5% in controls. Treated tumors exhibited extensive necrotic regions (pink, ghost-cell areas on H&E) and a reduction in viable tumor cells. No treatment-related mortalities occurred. Combination therapy was associated with a modest reduction in animal body weight (possibly reflecting added toxicity), whereas Q/C alone was well tolerated.

conclusionIn the PDAC xenograft model, Q/C (quercetin/curcumin) demonstrated antitumor activity, slowing tumor progression and increasing intratumoral necrotic areas compared to the control group; quantitative results are presented as mean differences with 95% confidence intervals (one-way ANOVA with Tukey post-hoc). Specifically, Q/C plus cisplatin showed the smallest tumors and the greatest regression compared to each of the monotherapies. These findings suggest that combining quercetin and curcumin may help counter tumor resistance and enhance healing. Q/C, a novel polyphenol formulation, appears promising as an adjunctive (and potentially alternative) therapy in pancreatic cancer. Further studies are required to elucidate its range of effects, broaden its interactions with standard therapies (yielding effects greater than those of either agent alone), and enhance its clinical applicability in overcoming the resistance to invasiveness of pancreatic cancer.