Open Access

In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2]

Simona Kranjc
Simona Kranjc
, 
Maja Cemazar
Maja Cemazar
, 
Gregor Sersa
Gregor Sersa
, 
Janez Scancar
Janez Scancar
 and 
Sabina Grabner
Sabina Grabner
   | Sep 14, 2017
Radiology and Oncology's Cover Image
About this article
Previous Article
Next Article
Cite
Article Category: Research Article
Published Online: Sep 14, 2017
Page range: 295 - 306
Received: Jul 20, 2017
Accepted: Aug 04, 2017
DOI: https://doi.org/10.1515/raon-2017-0034
© 2017 Simona Kranjc, Maja Cemazar, Gregor Sersa, Janez Scancar, Sabina Grabner
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Survival of SA-1 sarcoma (A), TBLCI2 sarcoma (B) and TBLCI2Pt sarcoma cells (C) after treatment with cisplatin (CDDP) or compound 2 or cisplatin electrochemotherapy (ECT CDDP) or compound 2 electrochemotherapy (ECT Compound 2), determined using a clonogenic assay. Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of triplicates pooled from three independent experiments. The survival of cells treated with electrochemotherapy was normalized to the survival of cells treated with electric pulses alone. The survival of SA-1, TBLCl2 and TBLCl2Pt cells treated with electric pulses alone was 0.96 ± 0.05, 0.93 ± 0.09 and 0.92 ± 0.10, respectively.
Survival of SA-1 sarcoma (A), TBLCI2 sarcoma (B) and TBLCI2Pt sarcoma cells (C) after treatment with cisplatin (CDDP) or compound 2 or cisplatin electrochemotherapy (ECT CDDP) or compound 2 electrochemotherapy (ECT Compound 2), determined using a clonogenic assay. Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of triplicates pooled from three independent experiments. The survival of cells treated with electrochemotherapy was normalized to the survival of cells treated with electric pulses alone. The survival of SA-1, TBLCl2 and TBLCl2Pt cells treated with electric pulses alone was 0.96 ± 0.05, 0.93 ± 0.09 and 0.92 ± 0.10, respectively.

Figure 2

Tumour growth and animal body weight change after cisplatin or compound 2 electrochemotherapy in mouse sarcoma tumours; SA-1, TBLCl2 and TBLCl2Pt. Mice (6-12 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mmol/kg) or compound 2 (13.3 mmol/kg) or with local application of electric pulses at 1 minute after drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of tumour volumes.*p (< 0.05) significant difference compared to treatment with cisplatin electrochemotherapy
Tumour growth and animal body weight change after cisplatin or compound 2 electrochemotherapy in mouse sarcoma tumours; SA-1, TBLCl2 and TBLCl2Pt. Mice (6-12 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mmol/kg) or compound 2 (13.3 mmol/kg) or with local application of electric pulses at 1 minute after drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of tumour volumes.*p (< 0.05) significant difference compared to treatment with cisplatin electrochemotherapy

Figure 3

Platinum amount in sarcoma SA-1 tumours (A), platinum amount in the serum (B) and platinum amount bound to DNA in the cells isolated from SA-1 tumours (C). Animals (8 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mM) alone or compound 2 (13.3 mM) alone or with local application of electric pulses 1 minute after intratumoural drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). The data are presented as the arithmetic mean and standard error of the mean (AM±SE) obtained from 8 samples. *p (< 0.05) under (A) and (C) statistically significant difference compared to corresponding drug treatment only; *p (< 0.05) under (B) statistically significant difference compared to cisplatin or cisplatin electrochemotherapy.
Platinum amount in sarcoma SA-1 tumours (A), platinum amount in the serum (B) and platinum amount bound to DNA in the cells isolated from SA-1 tumours (C). Animals (8 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mM) alone or compound 2 (13.3 mM) alone or with local application of electric pulses 1 minute after intratumoural drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). The data are presented as the arithmetic mean and standard error of the mean (AM±SE) obtained from 8 samples. *p (< 0.05) under (A) and (C) statistically significant difference compared to corresponding drug treatment only; *p (< 0.05) under (B) statistically significant difference compared to cisplatin or cisplatin electrochemotherapy.

Antitumour effectiveness of electrochemotherapy with cisplatin or compound 2 in mouse sarcoma tumours; SA-1, TBLCl2 and TBLCl2Pt

SA-1 TBLCl2 TBLCI2Pt
Group n DT (days) (AM±SE) GD (days) CR (n, %) n DT (days) (AM±SE) GD (days) CR (n, %) n DT (days) (AM±SE) GD (days) CR (n, %)
Control 10 1.7±0.2 0 8 2.8±0.3 0 6 3.1±0.2 0
EP 10 3.1 ±0.3 1.4 0 8 5.1±1.0 2.3 0 6 4.2±0.9 1.1 0
CDDP 10 5.2±1.0

p (< 0.05) significant difference compared to treatment with CDDP electrochemotherapy;

 3.5 0 8 5.3±0.7

p (< 0.05) significant difference compared to treatment with CDDP electrochemotherapy;

 2.5 0 6 3.4±0.5

p (< 0.05) significant difference compared to treatment with CDDP electrochemotherapy;

 0.3 0
Compound 2 12 2.3±0.3

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

 0.6 0 9 3.5±0.5

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

 0.7 0 6 3.2±0.3

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

 0.1 0
ECT CDDP 12 15.8±2.2

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

 14.1 0 9 11.6±1.0 8.8 6, 66.6 6 7.6±0.9

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

 4.5 0
ECT Compound 2 12 5.1±0.4 3.4 0 9 9.4±1.8 6.6 1, 11.1 6 5.1±0.6 2.0 0

IC50 values after electrochemotherapy with cisplatin or compound 2 in various mouse tumour cell lines

SA-1 TBLCI2 TBLCI2Pt
Group IC50 (μM) EF IC50 (μM) EF IC50 (μM) EF
CDDP 276.7

p (< 0.05) statistically significant difference compared to treatment with cisplatin electrochemotherapy (ECT CDDP);

 180.0

p (< 0.05) statistically significant difference compared to treatment with cisplatin electrochemotherapy (ECT CDDP);

 926.6

p (< 0.05) statistically significant difference compared to treatment with cisplatin electrochemotherapy (ECT CDDP);
Compound 2 500.0

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy (ECT Compound 2)

 220.0

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy (ECT Compound 2)

 1066.6

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy (ECT Compound 2)
ECT CDDP 28.3

p (< 0.05) statistically difference compared to treatment with compound 2 electrochemotherapy.

 9.8 8.0

p (< 0.05) statistically difference compared to treatment with compound 2 electrochemotherapy.

 22.5 12.0

p (< 0.05) statistically difference compared to treatment with compound 2 electrochemotherapy.

 77.2
ECT Compound 2 80.0 6.3 41.0 5.4 206.7 5.2
eISSN:
1581-3207
Language:
English
Publication timeframe:
4 times per year
Journal Subjects:
Medicine, Clinical Medicine, Internal Medicine, Haematology, Oncology, Radiology
Journal RSS Feed