Kisspeptin-10 Spray

Breast cancer is the malignant tumor with the highest incidence rate among women. TNBC is the core indication of KP-10 spray because of its lack of hormone receptor, HER2 negative, high metastasis rate (lung/liver/brain metastasis) and poor prognosis.
In vitro effect: For TNBC cells (MDA-MB-231, MDA-MB-157), KP-10 spray simulated administration (10-100nM) can inhibit cell migration by 60% -80%, reduce invasion by 70%, induce apoptosis by 40%, and reverse the EMT phenotype.

In vivo animal experiment: TNBC xenotransplantation mouse model, KP-10 nasal spray (100 μ g/spray, twice a day, lasting for 6 weeks), the number of pulmonary metastasis nodules reduced by 85% -95%, the inhibition rate of liver metastasis reached 80%, the tumor volume reduced by 40% -50%, and the survival period of mice prolonged by 30% -40%.
Clinical transformation potential: clinical samples confirmed that the positive rate of GPR54 expression in TNBC tissue was 65%, and the metastasis inhibition rate of KP-10 spray on GPR54 positive TNBC patients was significantly higher than that of negative patients, which can be used as an auxiliary treatment after surgery to prevent recurrence and metastasis.

Melanoma is the most malignant and rapidly metastasizing skin tumor, with early lung, liver, and brain metastases and a low 5-year survival rate. KISS1 gene was first found in melanoma. KP-10 spray has a strong natural inhibitory effect on melanoma metastasis.
Mechanism specificity: KISS1 gene is completely methylated and silenced in metastatic melanoma. KP-10 spray can activate demethylation signal through GPR54, restore endogenous KISS1 expression, form positive feedback of "exogenous KP-10 → endogenous KISS1 activation → metastasis inhibition", and effectively block metastasis.

In vivo effect: B16 melanoma lung metastasis mouse model, KP-10 aerosol inhalation spray (50 μ g/time, twice a day, 4 weeks), the number of lung metastasis nodules reduced by 90% -95%, almost completely blocking lung metastasis; The primary tumor growth inhibition rate is 50%, and there are no significant toxic reactions.
Clinical value: It can be used as an adjuvant therapy for melanoma after surgery to clear micro metastases; Or late stage palliative treatment can delay the progression of metastasis and prolong survival.

Endometrial cancer is a common malignant tumor in the female reproductive tract, which is prone to deep muscle infiltration, lymphatic metastasis, and distant metastasis in the late stage. Low expression of KISS1/GPR54 is closely related to poor prognosis. KP-10 spray inhibits endometrial cancer metastasis by inhibiting cancer cell invasion, blocking lymphatic angiogenesis, and reversing EMT.
In vitro effect: KP-10 can inhibit SDF-1-induced invasion (inhibition rate 70% -80%), reduce MMP-2 and MMP-9 activity, upregulate E-cadherin expression, and inhibit cell migration in endometrial cancer cells (Ishikawa, RL95-2).

In vivo effect: Endometrial cancer xenotransplantation model, KP-10 oral mucosa spray (100 μ g/time, twice a day, 6 weeks), lymph metastasis rate reduced by 60%, distant metastasis (lung/liver) inhibition rate reached 75%, and the depth of tumor invasion significantly reduced.
Clinical significance: It can be used for preventing lymphatic micrometastasis after early endometrial cancer surgery; Late stage combined radiotherapy and chemotherapy can enhance metastasis inhibition and improve prognosis.

Prostate cancer is prone to bone metastasis (with an incidence rate of 80%), leading to bone pain, fractures, spinal cord compression, and seriously affecting quality of life. KP-10 spray can inhibit prostate cancer bone metastasis by inhibiting prostate cancer cell invasion, blocking bone microenvironment chemotaxis, inhibiting osteoclast activity.

Mechanism characteristics: Prostate cancer cells highly express GPR54, and KP-10 can block CXCR4/SDF-1-mediated bone chemotaxis, inhibiting cancer cell migration to bone tissue; Simultaneously inhibiting osteoclast differentiation and activity, reducing bone destruction, and relieving bone pain.
In vivo effect: The prostate cancer PC-3 bone metastasis mouse model, KP-10 nasal spray (100 μ g/time, twice a day, 8 weeks), reduced the number of bone metastases by 70% -80%, significantly reduced the degree of bone destruction, alleviated the bone pain behavior of mice, and prolonged the survival period by 25%.

Chemotherapy is the main treatment for advanced tumors, but high doses are highly toxic, prone to drug resistance, and have poor efficacy in treating micro metastases. KP-10 spray combined with chemotherapy (cisplatin, paclitaxel, doxorubicin) can synergistically inhibit metastasis, sensitize chemotherapy, reduce chemotherapy dose and reduce toxicity.

Collaborative mechanism: KP-10 reverses EMT, restoring the sensitivity of drug-resistant cancer cells to chemotherapy drugs; Inhibit tumor angiogenesis and increase the enrichment of chemotherapy drugs in tumor tissues; Inducing cancer cell apoptosis and synergistically killing cancer cells with chemotherapy drugs.
Combined effect: In TNBC model, KP-10 spray+low-dose paclitaxel (1/2 conventional dose) can inhibit lung metastasis by 90%, which is superior to paclitaxel alone (50%) or KP-10 alone (70%); The dosage of chemotherapy drugs was reduced by 50%, the toxicity was reduced by 60%, and the survival of mice was extended by 40%.

Highly metastatic tumors (such as melanoma and TNBC) often have reduced sensitivity to KP-10 due to methylation silencing of KISS1/GPR54 genes. Combined with demethylation drugs (dexitabine, azacytidine), reversible transgenic methylation and up-regulated GPR54 expression significantly enhanced the transfer inhibition effect of KP-10 spray.

Sensitization mechanism: Demethylating drugs inhibit DNA methyltransferase, restore KISS1/GPR54 gene expression, and make cancer cells re express GPR54, increasing sensitivity to KP-10 by 3-5 times.
Combined effect: In the melanoma model, dexitabine+KP-10 spray, the inhibition rate of lung metastasis reached 95%, significantly higher than that of KP-10 alone (70%); The expression of GPR54 was upregulated by 4 times, and the apoptosis rate of cancer cells increased by 2 times.