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Docetaxel in combination with octreotide shows synergistic apoptotic effect by increasing SSTR2 and SSTR5 expression levels in prostate and breast cancer cell lines

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Abstract

Purpose

Docetaxel (DTX) is widely used for the treatment of metastatic prostate and breast cancers. Despite the clinical success of DTX, drug-related cumulative toxicity restricts its clinical use in cancer therapy. Thus, there is an urgent need for new therapeutic options. Octreotide (OCT) is a synthetic somatostatin analog that induces apoptosis in different cancer cell lines in vitro. In this study, we investigated the possible synergistic apoptotic effects of DTX in combination with OCT in prostate and breast cancer cell lines.

Methods

The XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by Cell Death Detection ELISAPlus Kit. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Levels of SSTR2 and SSTR5 proteins were determined by western blot analysis.

Results

DTX and OCT combination induced apoptosis in both breast and prostate cancer cells in a concentration- and time-dependent manner. Moreover, combination treatment resulted in inhibition of anti-apoptotic proteins such as Bcl-2 and Bcl-xL and induction of pro-apoptotic proteins Bax, Cytochrome c and IAPs in all of the tested cancer cell lines. SSTR2 and SSTR5 protein levels were induced as compared to any agent alone.

Conclusions

These results indicate that this combination treatment is a significant inducer of apoptosis in a synergistic manner in breast and prostate cancer cells. This strong synergism helps to lower the dose of DTX in both types of cancers, thus letting DTX to be used for longer periods by delaying resistance development and lesser side effects.

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Authors and Affiliations

  1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100, Bornova, Izmir, Turkey

    Burcak Karaca, Bulent Karabulut, Ulus Ali Sanli & Ruchan Uslu

  2. Department of Internal Medicine, Tepecik Training and Research Hospital, Izmir, Turkey

    Mustafa Degirmenci & Ahmet Ozveren

  3. Section of Molecular Biology, Department of Biology, Faculty of Science and Letters, Celal Bayar University, 45140, Muradiye, Manisa, Turkey

    Harika Atmaca & Emir Bozkurt

Authors
  1. Burcak Karaca
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  2. Mustafa Degirmenci
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  3. Ahmet Ozveren
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  4. Harika Atmaca
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  5. Emir Bozkurt
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  6. Bulent Karabulut
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  7. Ulus Ali Sanli
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  8. Ruchan Uslu
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Correspondence to Burcak Karaca.

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Karaca, B., Degirmenci, M., Ozveren, A. et al. Docetaxel in combination with octreotide shows synergistic apoptotic effect by increasing SSTR2 and SSTR5 expression levels in prostate and breast cancer cell lines. Cancer Chemother Pharmacol 75, 1273–1280 (2015). https://doi.org/10.1007/s00280-015-2756-1

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  • DOI: https://doi.org/10.1007/s00280-015-2756-1

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