Docetaxel in combination with octreotide shows synergistic apoptotic effect by increasing SSTR2 and SSTR5 expression levels in prostate and breast cancer cell lines.
OBJECTIVE
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 ELISA(Plus) 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.
Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100, Bornova, Izmir, Turkey, karacaburcak@hotmail.com.
Burcak
B
Karaca
Mustafa
M
Degirmenci
Ahmet
A
Ozveren
Harika
H
Atmaca
Emir
E
Bozkurt
Bulent
B
Karabulut
Ulus Ali
UA
Sanli
Ruchan
R
Uslu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000235:genetics; D000077143:Docetaxel; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008297:Male; D015282:Octreotide / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D043823:Taxoids; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000077143:Docetaxel; C094573:somatostatin receptor 5; D045304:Cytochromes c; D015282:Octreotide