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Curcumin enhances anti?cancer efficacy of either gemcitabine or docetaxel on pancreatic cancer cells.

ABSTRACT: Curcumin is a natural compound extracted from turmeric (Curcuma longa), which has been reported to be a promising anti?cancer drug in various human cancers. However, the effects of combination treatment of curcumin with gemcitabine or docetaxel on pancreatic cancer remains elusive. In the present study, the combinatory effects of curcumin with either gemcitabine or docetaxel on the proliferation, apoptosis, migration as well as invasion of PC cells were investigated. Calcusyn software was used to determine whether curcumin has is synergistic with gemcitabine or docetaxel. Combination index values from combinational use were all lower than 1, indicating the synergism of curcumin with gemcitabine or docetaxel on PC cells in vitro. EdU assay showed that curcumin could enhance the ability of gemcitabine or docetaxel to inhibit the proliferation of PC cells. Furthermore, the results from transmission electron microscope, DAPI staining experiments and western blot analysis revealed that curcumin may trigger apoptosis of PC cells via PARP/caspase?3 signaling pathway and reinforced pro?apoptotic ability of either gemcitabine or docetaxel. In addition, curcumin exhibited marked suppressive ability on metastasis of PC cells by wound healing and matrigel?transwell assay. Mechanistically, upregulation of TIMP1/TIMP2 with concomitant downregulation of MMP2/MMP9/N?cadherin proteins may be involved in this process. In conclusion, curcumin showed synergistic anti?cancer effects with either gemcitabine or docetaxel on PC cells.

SUBMITTER: Liu P

PROVIDER: S-EPMC7448442 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Curcumin enhances anti‑cancer efficacy of either gemcitabine or docetaxel on pancreatic cancer cells.

Liu Pan P Ying Qian Q Liu Huan H Yu Si-Qi SQ Bu Lu-Ping LP Shao Liang L Li Xin-Yi XY

Oncology reports 20200803 4

Curcumin is a natural compound extracted from turmeric (Curcuma longa), which has been reported to be a promising anti‑cancer drug in various human cancers. However, the effects of combination treatment of curcumin with gemcitabine or docetaxel on pancreatic cancer remains elusive. In the present study, the combinatory effects of curcumin with either gemcitabine or docetaxel on the proliferation, apoptosis, migration as well as invasion of PC cells were investigated. Calcusyn software was used t ...[more]

PMID: 32945513

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Project description:Purpose: Treatment of advanced pancreatic cancer with a single therapeutic at a maximal dose has been largely ineffective at increasing survival. Combination therapies are commonly studied but often limited by toxicity. We previously showed that low-dose multiagent therapy with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), and cisplatin (GTX-C) was safe, well tolerated, and effective (NCT01459614). Here, we hypothesize that adding irinotecan to GTX-C may improve survival with minimal toxicity. Experimental Design: Patients with treatment-naïve metastatic pancreatic adenocarcinoma were treated with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), cisplatin, and irinotecan (GTX-CI). Treatment consisted of capecitabine 500 mg twice daily on days 1–14 and gemcitabine 300 to 500 mg/m2, docetaxel 20 mg/m2, cisplatin 15 to 20 mg/m2, and irinotecan 20 to 60 mg/m2 on days 4 and 11 of a 21-day cycle. The primary objective was 9-month overall survival (OS). Secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and OS. Results: The regimen was well tolerated. The recommended phase II dose was gemcitabine 500 mg/m2, docetaxel 20 mg/m2, capecitabine 500 mg po bid, cisplatin 20 mg/m2, and irinotecan 20 mg/m2. Median follow-up in phase II was 11.02 months (2.37–45.17). Nine-month OS rate was 57% [95% confidence interval (CI): (41–77)]. RR was 57% [95% CI: (37–75) 50% PR and 7% CR]. DCR was 87% [95% CI: (69–96)]. Median OS and PFS were 11.02 [95% CI: (8.54–21.09)] and 8.34 [95% CI: (6.34–NA)] months, respectively. Conclusions: The addition of irinotecan to GTX-C was safe and well tolerated. While the study did not meet its primary objective, the responses were clinically meaningful using a well-tolerated regimen. Significance: We aimed to optimize the previously reported efficacious regimen of low-dose multiagent therapy with GTX-C for the treatment of metastatic pancreatic ductal adenocarcinoma by adding irinotecan. The primary objective was not met, but GTX-CI was well tolerated. The RR of 57%, median PFS of 8.3 months, median OS of 11 months, and 36-month OS rate of 19% suggest clinical benefit. Further optimization of this regimen is warranted.

Dataset Information

Curcumin enhances anti?cancer efficacy of either gemcitabine or docetaxel on pancreatic cancer cells.

Publications

Curcumin enhances anti‑cancer efficacy of either gemcitabine or docetaxel on pancreatic cancer cells.

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