Paclitaxel-octreotide conjugates in tumor growth inhibition of A549 human non-small cell lung cancer xenografted into nude mice

Abstract

Targeted chemotherapy is a novel approach to cancer therapies. This study evaluated the anti-tumor effects of conjugates made by coupling cytotoxic paclitaxel to the somatostatin analog octreotide in A549 human non-small-cell lung cancer (NSCLC) cells xenografted into nude mice. Two cytotoxic somatostatin analogs, paclitaxel-octreotide and 2paclitaxel-octreotide, were prepared by the coupling of one or two paclitaxel molecules with an octreotide molecule. A549 xenografts expressed mRNAs for type 1, 2, 4, and 5 somatostatin receptors. Immunohistology revealed that type 2 somatostatin receptors were mainly located in tumor cell membrane but type 5 somatostatin receptors were found in tumor cell membrane and cytoplasm.

Significant tumor growth inhibition was achieved by 2paclitaxel-octreotide at 150 nM/kg and 300 nM/kg. 2paclitaxel-octreotide also significantly extended the tumor doubling time and significantly reduced tumor microvessel density at these doses.

Moreover, there was more fragmented DNA in the 2paclitaxel-octreotide single and double dose groups than in the controls.

Paclitaxel was ineffective and more toxic than the conjugate as shown by the significant decline of body weight in Paclitaxel group on Days 6, 12, and 26 compared to those treated with 2paclitaxel-octreotide (P<0.05). White blood cell counts in the paclitaxel single and double dose groups were also significantly less than in the controls (P<0.05).

In conclusion, the targeting conjugate 2paclitaxel-octreotide made by coupling two molecules of cytotoxic paclitaxel to one somatostatin analog octreotide could enhance tumor growth inhibition and reduce toxicity in comparison to using the cytotoxic paclitaxel alone.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response.