J Cancer 2015; 6(4):360-366. doi:10.7150/jca.11308

Research Paper

Could Somatostatin Enhance the Outcomes of Chemotherapeutic Treatment in SCLC?

Kalliopi Domvri1, Dimitrios Bougiouklis2, Paul Zarogoulidis1✉, Konstantinos Porpodis1, Manolis Xristoforidis3, Alexandra Liaka1, Ellada Eleutheriadou1, Sofia Lampaki1, George Lazaridis4, John Organtzis1, George Kyriazis1, Wolfgang Hohenforst-Schmidt5, Katerina Tsirgogianni1, Vasilis Karavasilis6, Sofia Baka7, Kaid Darwiche8, Lutz Freitag8, Georgia Trakada9, Konstantinos Zarogoulidis1

1. Pulmonary Department-Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;
2. Gene and Cell Therapy Center, Hematology - BMT Unit, “G. Papanikolaou” Hospital, Thessaloniki, Greece;
3. Surgical Department “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;
4. Oncology Department, “G. Papageorgiou” Hospital, Thessaloniki, Greece.
5. II Medical Department, Regional Hospital of “Coburg”, Coburg, Germany.
6. Oncology Department, “G. Papageorgiou” University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
7. Oncology Department, “Interbalkan” European Medical Center, Thessaloniki, Greece.
8. University Pulmonary Department-Interventional Unit, University of Duisburg-Essen, Essen, Germany.
9. Department of Clinical Therapeutics, Division of Pulmonology, Medical School, National University of Athens, Athens, Greece.

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Domvri K, Bougiouklis D, Zarogoulidis P, Porpodis K, Xristoforidis M, Liaka A, Eleutheriadou E, Lampaki S, Lazaridis G, Organtzis J, Kyriazis G, Hohenforst-Schmidt W, Tsirgogianni K, Karavasilis V, Baka S, Darwiche K, Freitag L, Trakada G, Zarogoulidis K. Could Somatostatin Enhance the Outcomes of Chemotherapeutic Treatment in SCLC?. J Cancer 2015; 6(4):360-366. doi:10.7150/jca.11308. Available from http://www.jcancer.org/v06p0360.htm

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Purpose: Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Furthermore, somatostatin (SST) receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and are overexpressed in tumors. Since, human small-cell lung cancer overexpresses somatostatin receptors (STTR), they could be legitimate targets for treating SCLC.The aim of this study was the evaluation of cytotoxicity of somatostatin in combination with several anticancer drugs in HTB-175 cell line (Small Cell Lung Cancer Cell line that expresses neuron specific enolase).

Methods: Docetaxel, Paclitaxel, Carboplatin, Cisplatin, Etoposide, Gemzar, Navelbine, Fluorouracil, Farmorubicin are the chemotherapeutic drugs that we used for the combination before and after adding somatostatin in SCLC cell culture. HTB-175 cell line was purchased from ATCC LGC Standards.At indicated time-point, 48h after the combination, cell viability and apoptosis were measured with Annexin V staining by flow cytometry.

Results: Flow cytometry showed that Docetaxel, Paclitaxel, Gemzar and Cisplatin induced apoptosis more when they were added before somatostatin, whereas etoposide induced apoptosis more after somatostatin treatment. Navelbine alone or in combination with somatostatin showed no differences in apoptosis. Farmorubicin showed equal toxicity in all combinations. Fluorouracil and Carboplatin induced apoptosis more when added alone in HTB-175 cell line. However, increased apoptosis was also observed when Carboplatin was administered before somatostatin in higher concentrations.

Conclusion: Our results indicated that depending on the drug, somatostatin treatment before or after chemotherapeutic drugs increased apoptosis in small cell lung cancer cells. We suggest that long acting somatostatin analogues could be used as additive and maintenance therapy in combination to antineoplastic agents in SCLC patients.

Keywords: SCLC, somatostatin, lung cancer.