JPH01224319A - Cancer metastasis inhibitor - Google Patents
Cancer metastasis inhibitorInfo
- Publication number
- JPH01224319A JPH01224319A JP5053188A JP5053188A JPH01224319A JP H01224319 A JPH01224319 A JP H01224319A JP 5053188 A JP5053188 A JP 5053188A JP 5053188 A JP5053188 A JP 5053188A JP H01224319 A JPH01224319 A JP H01224319A
- Authority
- JP
- Japan
- Prior art keywords
- cancer
- cancer metastasis
- formula
- compound
- metastasis inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 201000011510 cancer Diseases 0.000 title claims abstract description 43
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 41
- 239000002257 antimetastatic agent Substances 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims description 7
- 206010027476 Metastases Diseases 0.000 abstract description 20
- 230000009401 metastasis Effects 0.000 abstract description 19
- YQOARHMNLCWEPG-DFTUVXBYSA-N 2,3-dimethoxy-5-methyl-6-[(2e,5e,7e,9r,10r,11e)-3,7,9,11-tetramethyl-10-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxytrideca-2,5,7,11-tetraenyl]-1h-pyridin-4-one Chemical compound O=C1C(OC)=C(OC)NC(C\C=C(/C)C\C=C\C(\C)=C\[C@@H](C)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C(\C)=C\C)=C1C YQOARHMNLCWEPG-DFTUVXBYSA-N 0.000 abstract description 17
- YQOARHMNLCWEPG-UHFFFAOYSA-N Glucopiericidin A Natural products COc1nc(CC=C(/C)CC=CC(=CC(C)C(OC2OC(CO)C(O)C(O)C2O)C(=CC)C)C)c(C)c(O)c1OC YQOARHMNLCWEPG-UHFFFAOYSA-N 0.000 abstract description 17
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- 210000002469 basement membrane Anatomy 0.000 abstract description 4
- 239000008187 granular material Substances 0.000 abstract description 3
- 244000005700 microbiome Species 0.000 abstract description 3
- 230000002792 vascular Effects 0.000 abstract description 3
- 238000002512 chemotherapy Methods 0.000 abstract description 2
- 208000024891 symptom Diseases 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- 239000010419 fine particle Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000001382 Experimental Melanoma Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 241000186361 Actinobacteria <class> Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 230000004712 cancer cell adhesion Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002700 inhibitory effect on cancer Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔発明の背景〕
〔産業上の利用分野〕
本発明は癌細胞の転移形成を顕著に阻害する癌転移阻害
剤に関する。さらに詳しくは、本発明は癌細胞の血管基
底膜成分への接着を阻害する作用を有するグルコピエリ
シジンAを含む癌転移阻害剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Background of the Invention] [Industrial Field of Application] The present invention relates to a cancer metastasis inhibitor that significantly inhibits the formation of metastases of cancer cells. More specifically, the present invention relates to a cancer metastasis inhibitor containing glucopiericidin A that has the effect of inhibiting the adhesion of cancer cells to vascular basement membrane components.
近年、癌の治療法は急速な進歩をとげてきた。 Cancer treatments have made rapid progress in recent years.
特に外科的手術又は放射線療法によって、原発癌の除去
に対する成功率が大幅に向上している。ところが、原発
癌の除去が完全になされても、癌の転移によって死に至
る場合が少なくなく、最近癌の転移阻+Lが癌治療上克
服すべき重要な問題であるとの認識が高まっている。In particular, surgery or radiotherapy has greatly improved the success rate for removing primary cancers. However, even if the primary cancer is completely removed, cancer metastasis often leads to death, and recently there has been increasing recognition that inhibition of cancer metastasis is an important problem to be overcome in cancer treatment.
転移は、原発部位からの癌細胞の遊離、脈管を介しての
移動、臓器脈管への接着、浸潤、更に増殖のプロセスを
含む複雑な現象であり、癌の特異的且つ重要な特徴であ
る。この癌転移は患者の予後を支配する重要な因子であ
るにもかかわらず、その研究は適当な実験系がないなど
からかなり遅れている。即ち、転移のメカニズムは、は
とんど解明されておらず、従ってその治療上の対応もは
とんどなされていないのが現状である。Metastasis is a complex phenomenon that involves the process of cancer cell release from the primary site, migration through blood vessels, adhesion to organ vessels, invasion, and further proliferation, and is a unique and important feature of cancer. be. Although cancer metastasis is an important factor governing patient prognosis, research on it has been delayed considerably due to the lack of suitable experimental systems. That is, the mechanism of metastasis has not been fully elucidated, and therefore, there are currently no therapeutic measures available.
従ってこの癌の転移をいかに阻止し、治療するかが、癌
の死亡率を低下させるのに極めて重要な課題である。癌
の転移を効果的に阻止する薬剤はほとんど現在のところ
は知られていない。本発明は、以上の技術課題に応える
癌転移阻害剤の提供が目的である。Therefore, how to prevent and treat cancer metastasis is an extremely important issue in reducing cancer mortality. Few drugs are currently known that effectively inhibit cancer metastasis. An object of the present invention is to provide a cancer metastasis inhibitor that meets the above technical problems.
〔課題を解決するための手段〕
最近になって、血管基底膜の細胞接着タンパク質である
ラミニンを部分分解した産物が転移を阻止するという報
告がなされてCrModulation o(’the
MetastaLic Activ4ty or M
elanoma Ce1l byLaiinin an
d Plbronectin J 、Victor P
、Terra−novaSJeannette E、
Williams 、 Lance A、Liotta
Georgc R,Martin : 5CIENC
E 22B (23) 982〜985 (1984
)]注目を集めた。これは、ラミニンの部分分解物が癌
細胞と血管基底膜ラミニンとの接着を阻害したためと考
えられている。[Means for solving the problem] Recently, it has been reported that a product obtained by partially decomposing laminin, a cell adhesion protein of the blood vessel basement membrane, inhibits metastasis.
MetastaLic Activ4ty or M
elanoma Ce1l by Laiinin an
d Plbronectin J, Victor P
,Terra-novaSJeannette E,
Williams, Lance A., Liotta
Georgc R, Martin: 5CIENC
E 22B (23) 982-985 (1984
)] attracted attention. This is thought to be because the partial decomposition product of laminin inhibited the adhesion between cancer cells and vascular basement membrane laminin.
そこで、本発明者は、癌細胞の接着を阻害する物質は転
移を阻害すると考え、広く天然界からこのような作用を
有する物質の探索を行なった。その結果、放線菌が生産
するグルコピエリシジンAが癌細胞の接着を強力に阻害
し、さらには癌転移阻害剤として有効であることを見出
して、本発明を完成するに至った。Therefore, the present inventor believed that a substance that inhibits adhesion of cancer cells would inhibit metastasis, and searched widely for substances that have such an effect from the natural world. As a result, the present inventors discovered that glucopiericidin A produced by actinomycetes strongly inhibits the adhesion of cancer cells and is also effective as a cancer metastasis inhibitor, leading to the completion of the present invention.
従って、本発明による癌転移阻害剤は、下式で表わされ
る化合物またはその薬学的に許容される塩を含有するこ
と、を特徴とするものである。Therefore, the cancer metastasis inhibitor according to the present invention is characterized by containing a compound represented by the following formula or a pharmaceutically acceptable salt thereof.
本発明の癌転移阻害剤グルコピエリシジンAは、試験管
内で癌細胞の接着を阻害する作用及び動物実験の実験転
移系で816マウスメラノーマ細胞の肺への転移阻止作
用を有する。Glucopiericidin A, a cancer metastasis inhibitor of the present invention, has the effect of inhibiting the adhesion of cancer cells in vitro and the effect of inhibiting the metastasis of 816 mouse melanoma cells to the lungs in an experimental metastasis system in animal experiments.
本発明の癌転移阻害剤グルコピエリシジンAは、これま
でまったく知られていなかった新しい作用機作、すなわ
ち癌細胞の接着阻害作用、に基づいて転移阻止効果を示
す薬剤であって、すぐれた癌治療薬となることが期待さ
れる。Glucopiericidin A, a cancer metastasis inhibitor of the present invention, is a drug that exhibits a metastasis inhibiting effect based on a new mechanism of action that was completely unknown until now, that is, an effect of inhibiting cancer cell adhesion, and is an excellent cancer metastasis inhibitor. It is expected that it will become a therapeutic drug.
〔グルコピエリシジンAおよびその製造〕本発明による
癌転移阻害剤の有効成分として使用するグルコピエリシ
ジンAは、それ自身公知の化合物である。[Glucopiericidin A and its production] Glucopiericidin A used as an active ingredient of the cancer metastasis inhibitor according to the present invention is a compound known per se.
すなわち、上記の構造式で示されるグルコピエリシジン
Aは、微生物の培養によって得られ、抗菌作用、降圧作
用、および免疫抑制作用を持つと報告されている。〔特
開昭61−210093号公報およびrNEV PfE
RICIDIN CLUCO8rDES。That is, glucopiericidin A represented by the above structural formula is obtained by culturing microorganisms, and is reported to have antibacterial, antihypertensive, and immunosuppressive effects. [Unexamined Japanese Patent Publication No. 61-210093 and rNEV PfE
RICIDIN CLUCO8rDES.
GIUCOPIRRICIDINS A AND BJ
、Masaru Matsumot。GIUCOPIRRICIDINS A AND BJ
, Masaru Matsumoto.
およびKln−1chi Mogi 、 KaLsuh
iko Nagaoka 5Seijl l5hize
ki、 Ryuichi KawaharaおよびTo
shi−aki NakashiIIla : TII
E JOURNAL OF ANTIBIOTIC8゜
XL(2)、 149〜1513 (1987))
この化合物は、従って、この公知の方法によって得るこ
とができ、また可能ならば全ないし半合成化学的な製造
法によってつくることができる。and Kln-1chi Mogi, KaLsuh
iko Nagaoka 5Seijl l5hize
ki, Ryuichi Kawahara and To
shi-aki NakashiIIla: TII
E JOURNAL OF ANTIBIOTIC8゜XL(2), 149-1513 (1987))
The compounds can therefore be obtained by this known method and, if possible, prepared by fully or semi-synthetic chemical production methods.
グルコピエリシジンAは分子構造が比較的に複雑である
ところから、全合成化学的な製造法よりも微生物学的な
製造法が実施しやすいといえようが、その場合に使用す
る微生物としては、前記公知方法で使用されているもの
の外に、本発明者らが、群馬県碓氷郡松井田町の土壌か
ら分離した放線菌であるに3320株(微工研菌寄第9
841号)を例示することができる。Since glucopiericidin A has a relatively complex molecular structure, microbiological manufacturing methods are easier to implement than total synthetic chemical manufacturing methods, but the microorganisms used in this case are: In addition to those used in the above-mentioned known method, the present inventors have isolated 3320 strains of actinomycetes from the soil of Matsuida-cho, Usui-gun, Gunma Prefecture (Feikoken Bacterial Collection No. 9).
No. 841) can be exemplified.
グルコピエリシジンAは、前記の構造式から判るように
、塩基性の窒素原子を有しているから、酸付加塩があり
うる。その場合の酸としては、三級窒素原子に付加して
塩を形成しつる任意の酸が使用可能である。本発明によ
るグルコピエリシジンAは癌転移阻害剤として使用され
′るところから、塩を形成させるべき酸は生理学上許容
されるものであることが望ましい。そのような酸は医薬
の分野で各種のものが知られており、最も典型的なもの
としては塩酸がある。As seen from the above structural formula, glucopiericidin A has a basic nitrogen atom, so it can be an acid addition salt. As the acid in this case, any acid that can be added to a tertiary nitrogen atom to form a salt can be used. Since glucopiericidin A according to the present invention is used as a cancer metastasis inhibitor, it is desirable that the acid with which the salt is to be formed be physiologically acceptable. Various types of such acids are known in the pharmaceutical field, the most typical of which is hydrochloric acid.
前記した通り、また後記の実施例2および3の結果によ
って証明されたように、グルコピエリシジンAは優れた
癌転移阻害剤として有用である。As described above and as evidenced by the results of Examples 2 and 3 below, glucopiericidin A is useful as an excellent cancer metastasis inhibitor.
本物質を癌転移阻害剤として用いる場合の投与量は、癌
の種類、患者の症状の程度なとにより異なっていて特に
制限はないか、通常は成人1日あたり20〜300mg
程度を1日1回程度、経口あるいは非経口的に投与する
。When using this substance as a cancer metastasis inhibitor, the dosage varies depending on the type of cancer and the severity of the patient's symptoms, and there is no particular restriction, and the dosage is usually 20 to 300 mg per day for adults.
Administer orally or parenterally once a day.
投与剤型としては、例えば散剤、細粒剤、顆粒剤、錠剤
、カプセル剤、注射剤などがあげられる。Examples of dosage forms include powders, fine granules, granules, tablets, capsules, and injections.
製剤化の際は、通常の製剤担体を用い、常法によって製
造することかできる。When preparing a formulation, it can be produced by a conventional method using a conventional pharmaceutical carrier.
本物質は、癌患者に治療剤として投与するほか、化学療
法、内分l・療法、免疫療法などの内科的治療、放射線
治療又は外科的治療により治療を終った患者の転移防止
に用いられる。In addition to being administered as a therapeutic agent to cancer patients, this substance is used to prevent metastasis in patients who have completed treatment with medical treatments such as chemotherapy, internal therapy, and immunotherapy, radiotherapy, or surgical treatment.
その際に、他の制癌剤と同時に服用させてももちろんよ
い。At that time, it is of course possible to take it simultaneously with other anticancer drugs.
なお、マウスに対する本物質の静脈投与における急性毒
性は、10mg/kg以上30mg/kg以下であると
報告されている〔前記J、AntibioLics、
XL(2)、 149〜15G (1987))。The acute toxicity of intravenous administration of this substance to mice is reported to be 10 mg/kg or more and 30 mg/kg or less [J, AntibioLics, supra.
XL(2), 149-15G (1987)).
下記の実施例は、本発明を説明するためのものである。 The following examples are intended to illustrate the invention.
本発明はこれらに限定されるものではない。The present invention is not limited to these.
実施例1: グルコビニリンジンAの調製aI溶性澱粉
1.596、グリセロール1,5%、大豆粉0. 5%
、魚粉1,5%、炭酸カルシウム0.2%の組成を有す
る液体培地をpH7,4とし500m1容イボ付三角フ
ラスコに100m1分注して滅菌する。これにに3B2
0株(微工研寄第9841号)を接種し、27°Cで4
日間振盪培養する。培養液800m1を酢酸エチル80
0m1で抽出し、溶媒を減圧留去して粗抽出物を得た。Example 1: Preparation of glucovinyrindin A aI soluble starch 1.596%, glycerol 1.5%, soybean flour 0. 5%
A liquid medium having a composition of 1.5% fish meal and 0.2% calcium carbonate was adjusted to pH 7.4 and sterilized by dispensing 100 ml into a 500 ml Erlenmeyer flask with warts. 3B2 to this
0 strain (Feikokenkyo No. 9841) was inoculated and incubated at 27°C for 4 hours.
Incubate with shaking for 1 day. 800ml of culture solution was diluted with 80ml of ethyl acetate.
The solvent was distilled off under reduced pressure to obtain a crude extract.
これをシリカゲル(メルク社製Kiesel Get
60 )カラムクロマトグラフィー3,0(φ)X30
cmに付しクロロホルム/メタノール(10:1)混液
で溶出した。グルコピエリシジンA画分20mgをセフ
ァデックスLH−20(ファルマシア社製)カラムクロ
マトグラフィー3.0(φ)X50cmに付し、メタノ
ールで溶出した。得られたグルコビニリンジン画分16
+ngをトヨパールHW−40(東洋リーダ社製)カラ
ムクロマトグラフィー3、O(φ)X50cmに付し、
メタノールで溶出してグルコピエリシジンAの純品9m
gを得た。紫外線吸収スペクトル、マススペクトル l
。This was mixed with silica gel (Merck Kiesel Get)
60) Column chromatography 3,0(φ)X30
cm and eluted with a chloroform/methanol (10:1) mixture. 20 mg of the glucopiericidin A fraction was subjected to Sephadex LH-20 (manufactured by Pharmacia) column chromatography, 3.0 (φ) x 50 cm, and eluted with methanol. Obtained glucobinyrindin fraction 16
+ng was applied to Toyopearl HW-40 (manufactured by Toyo Leader Co., Ltd.) column chromatography 3, O (φ) x 50 cm,
Pure glucopiericidin A 9m eluted with methanol
I got g. Ultraviolet absorption spectrum, mass spectrum l
.
NMRスペクトル、および”’C−NMRスペクトラル
にてこれがグルコピエリシジンAであることを確認した
。This was confirmed to be glucopiericidin A by the NMR spectrum and the "'C-NMR spectrum."
実施例2: B16メラノーマ細胞の接着に対する阻
害実験
ポリスチレン製のマイクロプレートウェルに20μg/
mlのラミニン溶液を加えて2時間室温に放置すると、
ウェルにラミニンかコートされる。Example 2: Inhibition experiment on adhesion of B16 melanoma cells.
Add ml of laminin solution and leave at room temperature for 2 hours.
The wells are coated with laminin.
これに816メラノーマ細胞10〜104個/well
を添加して37℃で2時間放置すると、ラミニンコート
ウェルには細胞が接着するか、無処理のウェルには接着
しない。この条件でグルコピエリシジンAを0.2μg
/ m1以上加えると、ラミニンコートウェルでも無
処理のウェルと同様に細胞は接着しなくなる。Add to this 816 melanoma cells 10-104 cells/well
When added and left at 37°C for 2 hours, cells either adhere to laminin-coated wells or do not adhere to untreated wells. Under these conditions, 0.2 μg of glucopiericidin A
/ml or more, cells no longer adhere to laminin-coated wells as well as untreated wells.
実施例3: B16メラノーマの肺転移系における実
験
BDF I雄マウスの尾静脈に1XIO4個のB16メ
ラノーマを移植する。そして210目にマウスを解剖し
、肺への転移の状況を観察した。Example 3: Experiment in B16 melanoma lung metastasis system BDF I male mice are implanted with 1XIO4 B16 melanomas in the tail vein. The mice were then dissected on the 210th day and the status of metastasis to the lungs was observed.
転移の状況は、転移の結節数をかぞえることによって行
なった。その値は、平均値±標準偏差(mean=!:
S D )で示した。なおマウスは1群8匹を用いた
。グルコピエリシジンAを各種方法にて投与して得られ
た結果は、以下に示す通りであった。少量の投与で50
%前後の癌転移阻害作用が認められた。The status of metastasis was determined by counting the number of metastatic nodes. The value is the mean ± standard deviation (mean=!:
S D ). Note that 8 mice were used per group. The results obtained by administering glucopiericidin A by various methods were as shown below. 50 with a small dose
An inhibitory effect on cancer metastasis of around 10% was observed.
Claims (1)
塩を含有することを特徴とする癌転移阻害剤。 ▲数式、化学式、表等があります▼[Scope of Claims] A cancer metastasis inhibitor characterized by containing a compound represented by the following formula or a pharmaceutically acceptable salt thereof. ▲Contains mathematical formulas, chemical formulas, tables, etc.▼
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5053188A JPH01224319A (en) | 1988-03-03 | 1988-03-03 | Cancer metastasis inhibitor |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5053188A JPH01224319A (en) | 1988-03-03 | 1988-03-03 | Cancer metastasis inhibitor |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH01224319A true JPH01224319A (en) | 1989-09-07 |
Family
ID=12861576
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP5053188A Pending JPH01224319A (en) | 1988-03-03 | 1988-03-03 | Cancer metastasis inhibitor |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH01224319A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011144115A (en) * | 2010-01-12 | 2011-07-28 | Gunma Univ | Chemotactic motion controller |
-
1988
- 1988-03-03 JP JP5053188A patent/JPH01224319A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011144115A (en) * | 2010-01-12 | 2011-07-28 | Gunma Univ | Chemotactic motion controller |
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