Combination methods of treating cancer
A cancer, subject technology, used in drug combinations, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve problems such as opportunistic infections
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Embodiment 1
[0246] Example 1 - Materials and methods
[0247] Chemicals:
[0248]Methyl jasmonate [methyl 3-oxo-2-(2-pentenyl)cyclopentaneacetic acid], 2-deoxy-D-glucose (2DG) were purchased from Sigma-Aldrich Chemie GmbH (Steinheim, Germany) , 1,3-bis{2-chloroethyl}-1-nitrosourea (BCNU) and cisplatinum(II) dichloride (cisplatin). Doxorubicin was purchased from Pharmacia Italia S.p.A and paclitaxel was purchased from MeadJohnson (USA). Methyl jasmonate was dissolved in absolute ethanol to obtain a 500 mM stock solution. Further dilute MJ and cytotoxic drugs in culture medium. The final concentration of ethanol in the culture did not exceed 0.6%. For in vivo experiments, doxorubicin was dissolved in phosphate buffered saline.
[0249] Tumor cell lines:
[0250] CT26 is a murine colon carcinoma. DA-3 is a murine mammary adenocarcinoma. TRAMP C1 is a murine prostate carcinoma. MCF7 is human breast cancer. MIAPaCa-2 is a human pancreatic carcinoma. D122 is murine lung cancer. ...
Embodiment 2
[0264] Example 2: Cytotoxic effect of MJ on tumor cell lines in vitro
[0265] The cytotoxic activity of MJ against 6 adherent cell lines and 1 ex vivo mouse cell line was tested in vitro. Each cell line was exposed for 24 hours with MJ at concentrations ranging from 0.1 mM to 2 mM, and cytotoxicity was determined as described in Methods. Table 1 summarizes the IC50 values. As shown in Figure 1, MJ at a concentration of 0.25 mM or higher exerted cytotoxic effects. All cell lines responded to MJ in a dose-dependent manner.
[0266] Table 1: IC50 of MJ in different cell lines
[0267] IC50 value MJ(mM) D122
Embodiment 3
[0268] Example 3: Cytotoxic effect of combination therapy of MJ and chemotherapeutic drugs on cancer cell lines in vitro
[0269] The synergistic effect of MJ and traditional chemotherapeutic drugs was examined. Anticancer agents are rarely used as monotherapy. Effective chemotherapy often relies on the appropriate and effective combination of two or more agents. Four drugs with different modes of action are selected. The synergy of the combination of BCNU, cisplatin, paclitaxel and doxorubicin with a fixed concentration of MJ was evaluated in 7 cell lines. Based on dose response data (Figure 1) the concentration of MJ was chosen such that the cytotoxicity of MJ did not exceed 40%. An interaction of MJ with another agent is considered to be positive when the difference between the cytotoxicity of the two drugs when they are present and the sum of the cytotoxicities produced by each drug administered alone (the expected additivity in the figure) is pV<0.05 Cooperative (supe...
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